Q2 2019 Earnings Call
Operator: Good afternoon, ladies and gentlemen, and welcome to the Syndax Second Quarter 2019 Financial Results Conference Call. At this time, all participants are in a listen-only mode.
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.
Operator: 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 then zero on your touchtone telephone. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Ms. Melissa Forrest of Argot Partners. Ma'am, please go ahead.
If anyone should require assistance during the conference. Please press the Star then zero on your Touchtone telephone.
Mine. During this conference call is being recorded I would now like to turn the conference over to your host less money. So far so good Barclays. Please go ahead.
Melissa Forrest: Welcome and thank you to those of you joining us on the line and the webcast this afternoon for a review of Syndax's second quarter 2019 financial and operating results. I'm Melissa Forster with Argo Partners, and with me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morris and Rick Shea, Chief Financial Officer. Also joining us on the call today for the question and answer session is Michael Metzger, President and COO, and Dr. Michael Myers, Chief Medical Officer.
I'm most support 'cause Argo partner 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 and [laughter].
Sure.
Also joining us on the call today, if the question and answer session is Michael Metzger, President and COO and Dr., Michael Myers, Chief Medical Officer.
Melissa Forrest: 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 the company's 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, the following statements are within the meaning of the Private Securities Litigation Reform Act of 1995. However, actual results may differ materially from those indicated by these statements as a result of various important factors. This includes those discussed in the risk factors section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the FBI. Any forward-looking statements represent the company's views as of today, August 7th, 2019. A replay of this call will be available on the website at www.syndax.com following the call. And with that, I'm pleased to turn the call over to Dr. Briggs-Morrison, Chief Executive Officer of Syndax.
This call is being accompanied by a slide deck has been posted on the company's website. So I would ask you to please turn to the company's 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.
To be honest.
Statements the meaning of the private Securities Litigation Reform Act of like <unk> actual results may differ materially from those indicated by these statements as a result of various important factors, which include those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q .
The other reports filed with the FCC any forward looking statements represent the company's views as of today August seven 2019.
A replay of this call will be available on the company.
Website at Www Dot dot dot com.
Following the call and with that I'm pleased to turn the call over to Dr. Briggs Morrison Chief Executive Officer.
Briggs Morrison: Thank you, Melissa, and thank you to everyone joining us on today's call and webcast. I'd like to start my comments by congratulating Michael Metzger, our President and Chief Operating Officer, on his appointment to the Board of Directors of Syndax. I have been fortunate to work with Michael over the past four years here at Syndax, and his appointment to the board is an important recognition of his many accomplishments and of his importance to the future of our company.
Thank you Melissa Thank you to everyone joining us on today's call and webcast.
I'd like to start my comments by congratulating, Michael Metzger, our President and Chief operating officer on his appointment to the board of directors of Syndax I've been fortunate to work with Michael over the past four years here its index and his appointment to the board isn't important recognition of his many accomplishments and that was important to the future of our company.
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.
Briggs Morrison: Slide 3 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. The exciting news from our second quarter was that the FDA cleared the IND for 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.
The exciting news from our second quarter or was that the FDA has cleared the I.N.D. for our highly selective rationally designed met inhibitor Essen Dx 56 13.
As a result of this accomplishment we are now entering a new and exciting chapter in the evolution of Sunday.
Briggs Morrison: We've spoken at length about our class 1 specific HDAC inhibitor, Intinistat, and our ongoing phase 3 trial of Intinistat in hormone receptor positive HER2 negative breast cancer. The new 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 Intendistat and SNDX5613 over the next 12 to 18 months. Let's review these opportunities in greater detail.
We've spoken at length about our class one specific h. dock inhibitor and kinda staff and our ongoing phase three trial of antennas that hormone receptor positive hertwo negative breast cancer.
The new SMB X 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 medicines.
We expect to know much more about the future prospects of both in tennis that and absent. The X 56 13 over the next 12 to 18 months.
Let's review these opportunities in greater detail.
Slide four summarizes the design of the phase three trial of antennas that hormone receptor positive hertwo negative breast cancer. The trial has randomized 608 patients to exit methane placebo versus ex the Mustang plus and Tenda stat and the focus of this trial is now clearly on overall survival.
Briggs Morrison: Slide 4 summarizes the design of the phase 3 trial of antinostat and hormone receptor positive per 2 negative breast cancer. The trial has randomized 608 patients to exomestane plus placebo versus exomestane plus antennastat, and the focus of this trial is now clearly on overall survival. As we've noted on previous calls, OS interim analyses are conducted by the ECOG Data Safety Monitoring Board approximately every six months.
As we've noted on previous calls our west interim analyses are conducted by the E. Com data safety monitoring board approximately every six months.
A positive outcome at any of these oh, its interim analyses or upon achieving the final number of events needed to conclude the study would allow us to file for regulatory approval in the United States based upon the terms of our breakthrough therapy designation in hormone receptor positive metastatic breast cancer and the special protocol assessment with the FDA.
Briggs Morrison: A positive outcome at any of these OS interim analyses or upon achieving the final number of events needed to conclude the study would allow us to file for regulatory approval in the United States based upon the terms of our breakthrough therapy designation for hormone receptor positive metastatic breast cancer and the 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 ECOP. I'd like to remind everyone that each interim analysis evaluates both the possibility that the trial is futile through a formal futility analysis at each interim, as well as the possibility that the trial is positive based on a statistically significant improvement in overall survival. The final analysis of this trial will be conducted once there are 410 events. The timing of which is uncertain.
Our team is prepared to submit a regulatory filing should the trial be positive within about six months are receiving the data from E com.
I'd like to remind everyone that each interim analysis evaluates both the possibility that the trial is few tile through a formal futility analysis at each interim as well as the possibility that the trial is positive based on a statistically significant improvement in overall survival.
The final analysis of this trial will be conducted once there are 410 events the timing of which is uncertain.
Briggs Morrison: We currently believe that the trial will fully read out in either November of this year or the first half of 2020. Slide 5 emphasizes the potential for the antinostat-examesting 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 a CDK4-6 inhibitor. Our current estimate is that between 30% and 50% of the patients in E2112 will have received a CDK4-6 inhibitor prior to entering the trial. Thus, we should have a highly relevant data set in the post-CDK-4.6 population. In our opinion, the rapid adoption of CDK4-6 inhibitors such as Ibran 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 Intinistat to enjoy similar widespread use.
We currently believe that the trial will fully read out either November of this year or the first half of 2020.
Slide five emphasizes the potential for the antennas that ex investing 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 a CDK four six inhibitor.
Our current estimate is that between 30 and 50% of the patients and 20 112 will have received a fee to K for six inhibitor prior to entering the trial.
Thus, we should have a highly relevant dataset in the post CDK four six population.
In our opinion the rapid adoption of CDK four 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 cancer therapies.
In the setting of a positive E. 20, 112 result, we would expect intend to start to enjoy similar widespread use.
This population of patients is substantial with an estimated 34000 patients each year, who go onto receive hormone therapy. After failing first line therapy, and who could therefore be eligible to receive the intent is that correct.
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 Intendacet. Let me now provide more detail about the news of the second quarter, the recent clearance of the IND for our genetically targeted agent, SNDX5613. Slide 6 shows the similarity between our Menin Program and other medicines that attack the fusion proteins that are the result of chromosomal rearrangement. We make this comparison because chromosomal rearrangements are a type of genomic alteration in cancer that has been highly predictive of clinical success when targeted therapies are used against it. The first example of a recurring chromosomal rearrangement in oncology was the so-called Philadelphia chromosome, which results in the BCR-ABL fusion protein. Gleevec and other BCR-ABL inhibitors have transformed the treatment of CML leukemias that harbor this fusion protein.
Let me now provide more detail about the news of the second quarter. The recent clearance of the I.N.D. for our genetically targeted agent Sn Dx 56 13.
[noise] flagship shows the similarity between our men in program and other medicines that attack that fusion proteins that the result of chromosomal rearrangement.
We make this comparison, because chromosomal rearrangements or a type of genomic alteration in cancer said about highly predictive of clinical success and targeted therapies are used against them.
The first example of recurring chroma somewhere rearrangement in oncology, but the so called Philadelphia chromosome.
Which results in the Bcr able fusion protein.
Gleevec and other Bcr able inhibitors have transformed the treatment of CML leukemias that harbor this fusion protein.
Briggs Morrison: Since then, there have been many examples of medicines that specifically attack fusion proteins that result from a chromosomal translocation. Including medicines like ALK fusions, Ntrek fusions, and Rett, In these chromosomal translocations, there is strong evidence that the resulting fusion protein is driving the cancer. Being able to precisely define these patients has led to the development of medicines that demonstrate large treatment effects in specific patient populations and enabled a rapid clinical development and regulatory path. It should be noted that in the examples I just mentioned, the resulting fusion protein was an activated kinase, and the drugs that were developed were kinase inhibitors. The signaling biology of the MLL rearrangement may in fact be distinct, and SNDX5613 is not a kinase inhibitor, so we of course need to see how 5613 behaves in the clinic.
Since then there have been many examples of medicines that specifically attack fusion proteins that result from a chromosomal translocation.
Putting medicines like al Fusions, and truck fusions and reperfusion.
And these chromosomal translocations there is strong evidence that the resulting fusion protein is driving the cancer cells.
Being able to precisely defined these patients led to the development of medicines that demonstrate large treatment effects in specific patient populations and enabled a rapid clinical development and regulatory path.
It should be noted that the examples I just mentioned, resulting fusion protein wasn't activated tiny and the drugs that were developed were kinase inhibitors.
Signaling biology of the MLL rearrangement may in fact be distinct and SMB X 56, 13 is not a kinase inhibitor. So we of course need to see how 56 13 behaves in the clinic.
Nonetheless, our 56 13 program as an example of a targeted therapy that was designed upon based upon our understanding of a specific chromosomal rearrangements that leads to a specific fusion protein known to drive the leukemic process.
Briggs Morrison: Nonetheless, our 5613 program is an example of a targeted therapy that was designed based upon our understanding of a specific chromosomal rearrangement that leads to a specific fusion protein known to drive the leukemic process. On slide 7, we summarize the first human trial in the Accelerated Understanding of Menin Inhibition, or AUGMENT, program. The first in human clinical trial is a combined phase 1 and phase 2 trial. The phase 1 portion is a dose escalation trial designed to identify the maximum tolerated dose and a recommended phase 2 dose for SNDX5613. Patients with relapsed or refractory acute leukemia will be enrolled and will take SNDX5613 daily by mouth until they experience either progressive disease or unacceptable toxicities. The first 28 days of dosing will serve as the period in which safety is evaluated for determining dose escalation. Patients are not required to have specific genetic abnormalities in order to enroll in the Phase 1 study. The first cohorts follow an accelerated dose titration with only one patient required per cohort. Upon entering a pre-specified level of toxicity, the trial will convert to a standard 3 plus 3 design.
On slide seven we summarize the first in human trial in the accelerated understanding of men inhibition or augment program.
The first in human clinical trial, its combined phase one and phase two trial.
The phase one portion is a dose escalation trial designed to identify the maximum tolerated dose and a recommended phase two dose for SMB X 56 13.
Patients with relapsed or refractory acute leukemia will be enrolled and will take a Sunday X 56, 13 daily by mouth until they experience either progressive disease for unacceptable toxicity.
The first 28 days of dosing will serve as the period in which safety is evaluated for determining dose escalation.
Patients are not required to have specific genetic abnormalities in order to enroll in the phase one study.
The first cohorts follow an accelerated dose titration with only one patient required per cohort.
Upon entering a pre specified level up toxicity the trial will convert to a standard three plus three design.
We will carefully assess pharmacokinetics safety and efficacy.
Briggs Morrison: We will carefully assess pharmacokinetics, safety, and ethics. It is anticipated that upwards of 30 patients may be enrolled in the Phase 1 portion, with the precise number dependent on the number of cohorts that need to be explored and the toxicities that are encountered. I want to emphasize that the PK analysis is a key component of the Phase 1 trial. Our preclinical data indicate that the menin-MLR interaction needs to be continuously inhibited in order to achieve optimal efficacy.
It is anticipated that upwards of 30 patients may be enrolled in the phase one portion with the precise number dependent on the number of cohorts that need to be explored and the toxicities that are encountered.
I want to emphasize that the PK analysis is a key component of the phase one trial.
Our preclinical data indicates that the men in MLL R interaction needs to be continuously inhibited in order to achieve optimal efficacy and so we'll be carefully examining the drug exposures in patients to assess whether we are indeed, achieving adequate tough target coverage.
We look forward to seeing this initial PK data in the first dose cohorts as those data will significantly and formed a likelihood and timing a single agent efficacy and the MLL rearranged and NPM want them, even leukemia population.
Briggs Morrison: And 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 this initial PK data in the first dose cohort, as those data will significantly inform the likelihood and timing of single agent efficacy in the MLL rearranged and NPM1 mutant leukemia population. Given that patients are not required to have a specific genetic abnormality 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 1 trial could bode well for establishing efficacy in the phase 2. Once a recommended Phase II dose is established, the Phase II 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 myeloid leukemia, or AML, adults with MLLR acute lymphoid leukemia, or ALL, and adults with NPM1 mutant AML.
Given that patients are not required to have a specific genetic abnormality 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 than the efficacy assessments with efficacy being an exploratory objective.
Furthermore, we believe that safely achieving adequate target coverage and the phase one trial could bode well for establishing efficacy in the phase two portion.
Once the recommended phase two dose is established the phase two trial will proceed to enroll three distinct expansion cohort.
Each of which consists of a specific genetically defined relapse or refractory acute leukemia.
The three cohorts are adult MLL R acute myeloid leukemia or AML.
Adults with MLL R acute lymphoid leukemia, or AOL and adults with MPM, one mutant AML.
The phase two portion will further characterize the safety of SMB X 56, 13 and will provide an initial estimate of the complete response rate as the primary measure of the therapeutic benefit.
We know that a lot of people are putting patients physicians and investors are eager to see the initial data from this first augment trial.
Given that we are just getting the trial up and running it is not possible to provide specific guidance as to when we will present data.
As of now we expect to report initial clinical data from the trial and 2020 and do not anticipate presenting data this year.
Briggs Morrison: The phase two portion will further characterize the safety of SNDX5613 and will provide an initial estimate of the complete response rate as the primary measure of the therapeutic benefit. We know that a lot of people, including patients, physicians, and investors, are eager to see the initial data from this first phase trial. Given that we are just getting the trial up and running, it is not possible to provide specific guidance as to when we will present data. As of now, we expect to report initial clinical data from the trial in 2020 and do not anticipate presenting data this year. We should be able to give you a better sense of data timing once the trial is underway. In addition, we are eager to advance this molecule into the pediatric population. It is a key component of our overall strategy.
We should be able to give you a better sense of data timing once the trial is underway.
In addition, we are eager to advance this molecule into the pediatric population. It is a key component of our overall strategy. We will have more to say about the details of the pediatric timing and approach on a future call.
Based upon preclinical data and the underlying biology or 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 past taken for ages addressing patients with split three or IDH one mutation.
That's continued to learn more about the potential of SMB X 56, 13 in acute leukemia.
Briggs Morrison: We will have more to say about the details of the pediatric timing and approach on a future call. 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 FLT3 or IDH1 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 patients with these syndromes.
We see this molecule, becoming an additional and important value driver for syntax.
Let me now turn to slide eight and Essen Dx 60, 350 to our potential best in class monoclonal antibody therapy targeting the CSF one receptor.
We're conducting a trial testing 60 352 as monotherapy in chronic gvhd.
Chronic gvhd is a frequent complication of amount of politics stem cell transplantation.
Wherein donor derived immune cells contribute to the initiation and development of fibrosis and manifestation of many of the advanced disease symptoms.
In preclinical models blockage of the CSF, one CSF, one our interaction with an anti CSF oner antibody can result in the depletion of donor macrophages, they are preventing and reducing chronic graft versus host disease.
Briggs Morrison: Let me now turn to slide 8 and SNDX6352, our potential best-in-class monoclonal antibody therapy targeting the CSF1 receptor. We're conducting a trial testing 6352 as monotherapy and chronic GVHD. Chronic GVHD is a frequent complication of hematopoietic stem cell transplantation, wherein donor-derived immune cells contribute to the initiation and development of fibrosis and manifestation of many of the advanced disease symptoms. The preclinical model's blockage of the CSF1-CSF1R interaction with an anti-CSF1R antibody can result in the depletion of donor macrophages, thereby preventing When our IND was cleared for this study, 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 slower than anticipated.
We believe the chronic graft versus host these represents an attractive clinical opportunity for 60 352.
When our idea was cleared for this study FDA required that we limit enrollment to patients whose disease had progressed after both steroids and I Bruton IV therapy.
However, as I Bruton, it's not currently frequently used to treat this population enrollment has been slower than anticipated.
We hope to provide an update on this program in the second half of next year. Despite our earlier guidance for later this year.
Finally, slide nine summarizes transactions that led to the acquisition of the men in MLL R and Ssds 53 52 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 to valuable inflection points and expect to me rain among preferred partners such transactions.
Briggs Morrison: We hope to provide an update on this program in the second half of next year, despite our earlier guidance for later this year. Finally, slide 9 summarizes the transactions that led to the acquisition of the Mennon MLR and SNDX 6352 programs. 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 to valuable inflection points and expect to remain among preferred partners in such transactions. I will now turn the call over to Rick to review our financial results.
I will now turn the call over to Rick to review our financial results.
Thank you Briggs.
Results of our operations for Q2, 2019, and the comparison to the prior year period 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 filed this afternoon.
Turning to slide 10.
We ended the second quarter of 2019 with $80.5 million in cash and 31.6 million shares in share equivalents outstanding.
Looking ahead I'd like to provide updated financial guidance for both Q3 and for the full year 2019.
Rick Shea: Thank you, Briggs. Results of our operations for Q2 2019 and the comparison to the prior year period 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 this afternoon. Turning to slide 10.
For the third quarter of 2019, we expect R&D expenses.
To be $11 million to $12 million and total operating expenses to be $15 million to $16 million.
And that includes approximately one and a half a million dollars of non cash stock compensation expense.
For the full year 2019, our guidance is substantially unchanged.
Rick Shea: We ended the second quarter of 2019 with $80.5 million in cash and 31.6 million shares and share equivalents outstanding. Looking ahead, I'd like to provide updated financial guidance for both Q3 and for the full year 2019. For the third quarter of 2019, we expect R&D expenses to be $11 to $12 million and total operating expenses to be $15 to $16 million. That includes approximately $1.5 million of non-cash stock compensation expenses. For the full year 2019, our guidance is substantially unchanged. We expect R&D expenses of $45 to $47 million and total operating expenses of $60 to $63 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. Our current cash, along with reduced spending, will allow us to operate the company to achieve key milestones for prioritized programs, specifically, OS results for E2112 and early proof of concept for our targeted menin inhibitors. We anticipate our year-end cash balance to be about $55 million.
We expect R&D expenses of $45 million to $47 million and total operating expenses of $60 million to $63 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 $52 million to $54 million.
Our current cash along with reduced spending will allow us to operate the company to achieve key milestones for a prioritized program specifically.
Oh, yes results for each 20, 112 and early proof of concept for our targeted men inhibitor.
We anticipate our year end cash balance.
To be about $55 million.
I would now turn the call back over to Briggs.
Thanks, very much Rick led to close our call with a clear summary of our company priorities.
I believe that a positive test result can he 20 112 would be transformative for synnex and create significant shareholder value.
We expect a final read out either in November of this year or the first half of 2020.
We also believe that SMB X 56, 13, our men and an L.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 single agent activity in patients with leukemia, providing clinical proof of concept and enabling early regulatory clarity and planning for next step.
Briggs Morrison: I would now turn the call back over to Briggs.
Operator: Thanks very much, Rick. I'd like to close our call with a clear summary of our company priorities. We believe that a positive O.S. result in E2112 would be transformative for Syndax and create significant shareholder value. We expect a final readout either in November of this year or the first half of 2020. We also believe that SNDX5613, our menin MLR inhibitor, is well-poised for near-term proof-of-concept data. We believe that safely achieving adequate target coverage in the Phase I trial could de-risk this program, with single-agent activity in patients with leukemia providing clinical proof-of-concept and enabling early regulatory clarity and planning for next steps. For SNDX 6352, we're expecting initial efficacy data in chronic GVHD in the second half of next year. 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 is a core strength of our company. As always, I'd 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.
Bresson Dx 60, 352 were expecting initial efficacy data in chronic gvhd and the second half of next year.
Finally, we are optimistic that we will continue to identify and bringing novel molecules to deepen our portfolio. We have a proven track record of delivering on this pillar of our strategy I believe this is a core strength of our company.
As always I'd like to thank the team here at Synta.
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 for questions.
Ladies and gentlemen, if you have a question at this time. Please press Star then the number one key on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the pound key.
You have your first question, Sir from Chris Shibutani of Cowen Your line is open.
Hi, guys. This is <unk> on for Chris Youve economy, we have a couple of questions.
Bert and Etwenty, one well have you guys done any recent modeling superjack, whether a positive result is more likely to occur in November versus day, and secondly on Dominion programs, how would the potential target population size compare with that FLT three or IDH targeted drugs. Thank you.
Operator: Ladies and gentlemen, if you have a question at this time, please press the star and then the number one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. We have your first question, sir, from Krishna Bhatani of Cowan. Your line is open. Hi guys, this is Pam Barrett on behalf of Krishi Bhatani. We have a couple of questions. First, on E2112, have you guys done any recent modeling to project whether a positive result is more likely to occur in November versus May? And secondly, on the Mennon Program, how would the potential target population size compare with that of FLT3 or IDH targeted drugs? Thank you.
Great. Thanks, so much maybe I'll, let Michael Myers talk about.
Our recent modeling as of November versus me, yes. So we actually are very optimistic that either the November or may analyses would yield a positive result.
And for all intensive purposes.
The profitability.
Either one of those two.
Now, let's see is approximately equal.
And your second question in terms of population size the.
MLL ours are roughly the same size as IDH two I don't have the three numbers in front of me right now.
Michael Werner Schmidt: Great, thanks so much. Maybe I'll let Michael Myers talk about our recent modeling of November versus May.
The other point I guess I would just emphasize NPM. One is of course larger represents probably about a third of AML.
Got it very helpful. Thanks.
Michael Werner Schmidt: We are actually very optimistic that either the November or May analyses would yield a positive result. And for all intents and purposes, the probability of success at either one of those two analyses is approximately equal.
[noise].
Your next question for Sundries comes from the line of Matt Do Kumar our your W. Baird. Your line is open.
Yeah, guys. Thanks for taking my questions. So first one about the Mad men and MLL program. How do you think about T.K. and potential differences in PK between MLL rearranged non rearranged patients, but can you can imagine for example that the non rearrange patients. If they just don't have the target and significant abundance are going to have a different PK profile than patients who have an abundance of that interaction kind of ramping up and then I'll have a follow up question after that.
Briggs Morrison: And your second question, in terms of population size, the MLLRs are roughly the same size as IDH2. I don't have the three numbers in front of me right now. The other point I guess I would just emphasize is NPM1 is, of course, larger. It represents probably about a third of AM.
Briggs Morrison: Got it. Very helpful. Thank you. Your next question presenter comes from the line of Madhu Kumar for RUW Baird. Your line is open. Yeah, guys, thanks for taking my question.
Right. So I think we would do the preclinical data we have so far would suggest that the exposure is needed to give efficacy whether its MLL R or NPM. One are roughly the same so because they are driven by the men in MLL R.
Briggs Morrison: So, first one about the MEN and MLL program: how do you think about PK and potential differences in PK between MLL rearranged patients and non-rearranged patients? Like, you could imagine, for example, that non-rearranged patients, if they just don't have the targeted and significant abundance, are going to have a different PK profile than patients who have an abundance of that interaction kind of ramping up.
The the MLL one men in interaction that's the the interaction that has to be disrupted and it appears that the the target exposures that are needed to disrupt that are the same whether it's.
Briggs Morrison: Right, so I think, Madhu, the preclinical data we have so far would suggest that the exposures needed to give efficacy, whether it's MLLR or NPM1, are roughly the same. So because they're driven by the Menin-MLLR, the MLL1-Menin interaction, that's the interaction that has to be disrupted, and it appears that the target exposures that are needed to disrupt that are In tumors that are neither one of those two genetically defined tumors, leukemias, our current evidence would suggest that the drug actually doesn't have activity in things where you don't have either NPM1 mutations or MLLR mutations.
NPM, one or MLL R.
In tumors that are neither one of those two genetic.
Genetically defined lead tumors <unk> leukemias.
Our current evidence would suggest that the drug actually doesn't have activity and things where you don't have either NPM wanted mutations or MLL R mutation.
Okay little bit in following from that point, if it doesn't have activity would you expect to have the same exposure dynamics as it would in a MLL R. NPM one.
Blood cancer.
Right. So I'm not entirely sure I get your question I mean, I think in terms of plasma exposures, whether you're in normal healthy volunteers or you're in cancer patients depending on what the cancer patient have shouldn't matter. That's just a PK characteristic of the drug.
Briggs Morrison: Okay, so then following from that point, if it doesn't have activity, would you expect it to have the same exposure dynamics as it would in an MLLR or NPM1 mutant blood cancer?
The question of whether they can disrupt the men in MLL interaction.
In our view really only as relevant in the MLL R population or the NPM one mutant population.
Briggs Morrison: Right, so I'm not entirely sure I understand your question. I mean, I think in terms of plasma exposures, whether you're normal healthy volunteers, or you're in cancer patients, depending on what the cancer patients have shouldn't matter. That's just a PK characteristic of the drug. The question of whether they can disrupt the Menin-MLL interaction, in our view, really only is relevant in the MLLR population or the NPM1 mutant population.
Okay, so to get to that to that point.
What is a good PD biomarker to show disruption of the men in MLL interaction.
Is that the one you put an employee in in kind of the expansion cohorts.
Yeah, I think it's we haven't said much about only was it anything at all about the Pharmacodynamic marker that we're using and we can talk about that and on future calls as that comes together.
Okay, great. Thanks.
Your next question is from David Lebovitz from Morgan Stanley . Your line is open.
Briggs Morrison: Okay, so to that point... What is a good PD biomarker to show disruption of the MEN and NLL interaction? And is that the one you plan on employing in kind of the expansion cohorts?
Oh, Thank you very much for taking my question just a.
Piggy back on an earlier question.
Regarding E 211 too.
I guess should we assume that the the powering between the November and May interim analyses are essentially a interim and final analyses are essentially the same.
Briggs Morrison: Yeah, I think it's, we haven't said much about, I don't think we've said anything at all about the pharmacodynamic marker that we're using, and we can talk about that on future calls as that comes together.
I'll give that question to Mike Meyers, our Chief Medical Officer.
Briggs Morrison: Okay, great. Thanks. Your next question is from David Lebovitz from Morgan Stanley. Your line is open. Thank you very much for taking my question.
Obviously, the greatest power is with the final analysis because it includes more more events. However, I think that at this point the number of events is not is not so great in terms of the difference between the two analyses that the power increases materially.
Michael Werner Schmidt: Just to piggyback on an earlier question regarding E2112, should we assume that the powering between the November and May interim analyses are, essentially, the same?
Okay.
Make sense.
Michael Werner Schmidt: I'll give that question to Michael Myers, our Chief Medical Officer.
And I guess, just jumping over to the men and program.
Hi, how are you.
Briggs Morrison: Obviously, the greatest power is with the final analysis because it includes more events. However, I think that at this point, the number of events is not so great in terms of the difference between the two analyses that the power increases materially. Okay, that makes sense. And I guess I'm just jumping over to the Mennon Program. As far as the tumors that were selected in this study, I would like to know a little bit about the rationale behind these specific tumors. Were there other tumors that you considered adding to the trial as well?
As far as the tumors that were selected in this study I guess, a little bit about the rationale behind these specific tumors, where there other tumors that you considered adding into the trial.
As well.
Right. So I think the MLL R population.
The basic biology that led to the to the invention of this molecule was all driven by the MLL R.
Briggs Morrison: Right, so I think the MLLR population, the basic biology that led to the invention of this molecule, was all driven by the MLLR chromosomal translocations, and so there the science is very well worked out that the aminotermers of MLLR1 need to bind to menin, that's really required for transformation, and if you disrupt that with a small molecule, you get antilochemic effects. So that's where the MLLR population is sort of the core scientific hypothesis of how the drug was developed. The NPM1 mutant population was identified by an academic group who noted that the transcript profile for NPM1 mutant leukemias looked very, very similar to the MLLRs, and so they tested NPM1 PDXs, and we saw really quite dramatic efficacy in those PDX models, so that's how we got those two.
Chromosomal translocations and so there the science is very well worked out that the amino terminus of MLL one needs to bind to men, that's really required for transformation and if you disrupt that with a small molecule you get anti leukemic effects. So that's where the MLL R population is sort of the core.
Scientific hypothesis of of how the drug was developed the NPM. One mutant population was identified by academic group, who noted that the.
A transcript profile for NPM, one muting leukemias looks very very similar to the MLL ours and so they tested NPM MPM one pbxs.
And we see really quite dramatic efficacy in those pdx models. So that's how we got those two.
That same group has tested molecule and other forms of leukemia and has not seen.
Briggs Morrison: That same group has tested the molecule in other forms of leukemia and has not seen activity, and so for now, we're not exploring those. However, there have been reports in the literature about the drug being used in some solid tumors. In our hands, we've not been able to repeat or confirm that efficacy in solid tumors. So at this point, based upon the experiments we've done with our molecule, we believe that MLLR and NPM1 are the ones that seem to have very, very strong preclinical data, and that's why we're pursuing them.
Activity and so for now we're not exploring those.
There have been reports in the literature about the drug being used in some solid tumors.
Uh huh.
In our hands, we've not been able to repeat or confirm that efficacy in solid tumors.
So at this point based upon the experiments weve done with our molecule. We believe that the MLL R and NPM. One are the ones that seem to have very very strong preclinical data and that's why we're pursuing them.
Thanks for taking my questions.
Briggs Morrison: Thanks for taking my questions. Your next question is from Buryat Hazalev from BTIG. Your line is open. Yeah, just a couple on MLL, the meta-inhibitor program, just brings a little bit more, if you could, as to why you're enrolling patients in terms of study design, why you're having patients that are not required to have a genetic abnormality in the first trial. First part of the
Your next question is from various hazlett from BTI to your line is open.
Yes, just a couple on MLL or the Oh I'm in a good program I'm just.
Brings a little bit more if you could as to why you're enrolling patients in terms of study design. While you were having patients that are not required to have a genetic abnormality in the b or the first trial.
First quarter going out yeah, I'll, let Michael Myers answer that question I would share that it was at the urging of via the day that we include patients who did not necessarily have the genetic abnormality.
Michael Werner Schmidt: Yeah, I'll let Michael Myers answer that question.
Briggs Morrison: Yeah, I would share that it was at the urging of the FDA that we included patients who did not necessarily have the genetic abnormality in order to better understand PK and safety. We fully expect, though, that the population may be enriched for the patients who are most likely to benefit, i.e. those who have the genetic abnormality. Okay, thank you. And then, are you starting at doses where you would expect to see activity in the initial cohorts?
In order to better understand the PK and safety.
Okay and then.
We fully expect though that the the population may be a rich for the patients who are most likely to benefit those who have the genetic abnormalities.
Okay. Thank you.
And then are you starting at doses, where you would expect to see activity in the initial cohorts.
Briggs Morrison: Right, so I think, Bert, that's what I was trying to get at in terms of the PK exposures in the Phase 1 portion. You know, we do this modeling of what we think human exposures are going to be, and based upon that modeling, we think we're not far off from those exposures, but you never really know until you actually start dosing patients. And so that's why I made the comment in my prepared remarks that seeing the exposure data from the first couple of cohorts will give us a much better sense of where we are. Okay.
Right. So I think Bert that's what I'm trying to get at in terms of the PK exposures in the phase one portion.
We do this modeling of what we think human exposures are going to be and based upon that modeling. We think we're not far off from exposures, but you never really know until you actually start dosing patients and so that's why I made the comment in my prepared remarks that seeing that exposure data from the first couple of cohorts will give us a much better sense of where we are.
Okay, and then just to be clear is there an ability to expand into every cohort into all cohorts. If you see activity in each one of the three.
Briggs Morrison: And then, just to be clear, is there an ability to expand into every cohort and into all cohorts if you see activity in each one of the three?
So the phase one portion really is just a defined that recommended dose and then we will expand into all three cohort.
Briggs Morrison: So the phase one portion really is just to define that recommended dose, and then we will expand into all three cohorts. Obviously, as Michael has pointed out, if the Phase I portion is a bit enriched, we get some of the patients with genetically defined lesions. That might give us an earlier view of efficacy, but the sort of, if you will, definitive assessment is really in the Phase II portion, and all three cohorts will be opened in parallel. I can't wait to see the data. Thank you.
Obviously as as Michael has pointed out if the trial if the phase one portion is a bit enriched we get some of the patients with the genetically defined lesions that might give us an earlier.
View of efficacy, but the the sort of if you will definitive assessment is really in the phase two portion and all three cohorts will be opened in parallel.
Great can't wait to see the data. Thank you.
Briggs Morrison: Can't wait to see the data. Thank you. Your next question is from Christopher Morai from Nomura Internet. Your line is open. Hello, this is Jackson Harvey on behalf of Christopher Mirai.
Your next question is from Christopher MRI from Nomura Instinet. Your line is open.
Hello. This is Jackson Harvey on for Christopher MRI. Thanks for taking my question I'm curious about the PK if the drug it looks like in some of the early pre clinical experiments and animals in may if needed twice daily dosing.
Briggs Morrison: Thanks for taking my question. I'm curious about the PK of the drug. It looked like in some of the early preclinical experiments in animals, it may have needed a twice daily dose. Can you speak a little bit about what you've seen in animal models for 5613 and also if you could give some insight into what dose limiting toxicities may look like based on those experiments? Thank you.
Can you speak a little bit about what you've seen in animal models for.
For 56, 13, and also if you could give some insight into what dose limiting toxicities may look like based on those experiments. Thank you.
Right. So Jackson just to be clear that the protocol does the phase one protocol does start with be I'd dosing. It has built into it the opportunity to look at other dosing regimens as well. So it goes to my earlier comment that we try to predict what the PK exposure will be and what the half life will be but we won't know that really until we start dosing patients. So we are starting with B.I.D. dosing and then we'll explore other regimens depending on the PK in terms of dose limiting toxicities in the preclinical work that data has not been presented yet should be presented at an upcoming.
Briggs Morrison: Right, so Jackson, just to be clear, the phase one protocol does start with BID dosing, but it has built into it the opportunity to look at other dosing regimens as well, so it goes to my earlier comment of, you know, we try to predict what the PK exposure will be and what the half-life will be, but we won't know that really until we start dosing patients. So we are starting with BID dosing, and then we'll explore other regimens depending on the PK. In terms of dose-limiting toxicities in preclinical work, that data has not been presented yet. It should be presented at an upcoming scientific congress. So that's about all I can say about the preclinical toxicology data.
Scientific Congress.
So that's about all I can say about about the preclinical tox data.
Your next question is from Hershey to Polish Paddy of B. Riley FBR. Your line is open.
Briggs Morrison: Your next question is from Hershey Depolichetty of B. Rowling FBR. Your line is open. Hello, this is Geoffrey Tan, on behalf of Harshita, and thanks for taking our questions. With regard to the menin inhibitor, I was curious if you've started to investigate possible resistance mechanisms that could emerge with the drug.
Hello. This is Jeffrey town on for her she does and thanks for taking our questions with regard to them in an inhibitor I was curious if you started to investigate possible resistance mechanisms that could emerge with the drugs.
Right. Thanks for the question, we have tried to start to explore this next month. The problem is we don't seem to be able to generate resistant mute.
Briggs Morrison: Right, thanks for the question. We have tried to start to explore resistant medicine. The problem is we don't seem to be able to generate resistant mutants. So, the team has tried some of the standard approaches where you treat, you stop treating, let the tumor come back, and treat again. The tumors seem to be continually sensitive. So, until we can actually identify resistant cell lines, we can't identify the mechanism. Of course, in patients, should we be fortunate enough to see patients respond, if those responses progress at a later time, we'll be able to look at that in samples from patients. But in preclinical models, we have not yet been able to generate resistant cells.
So the team has tried some of the standard approaches where you treat you stopped treating let the tumor go back treat again the tumors seem to.
Be continually sensitive so until we can actually identify resistant.
Cell lines, we can identify the mechanism.
Of course in patients should we be fortunate enough to see patients respond.
If those responses.
Progress at a later time, we'll be able to look at that in samples from patients, but in preclinical models, we have not yet been able to generate results.
And a second I know you previously guided to possible regulatory pathways as seen with the MTR cut in Alcs fusions for the men and molecule.
Briggs Morrison: And second, I know you've previously guided us to possible regulatory pathways as seen with the NTRK and ALK fusions for the menin molecule. Can you give us any additional color on that regulatory pathway?
Can you give us any additional color on that regulatory pathway.
Well, so again I think if you look at.
Briggs Morrison: Well, so, again, I think if you look at... Both the IDH programs, the FLIT III programs, direct fusions, you know, if you're seeing a reasonable level of complete response, in the case of leukemia, durable, complete responses, then, you know, the number of patients that you need is, you know, a bit more limited, and again, I'd encourage you just to take a look at some of the precedents from IDH programs, FLIT III programs, about sort of how many patients you need, and, you know, what level of activity was sufficient for them to get approved.
Both the IDH programs for three programs Trk Fusions, you know if you're seeing a reasonable level of complete response in the case of leukemia complete durable complete responses.
Then you know that the number of patients that you need.
It is.
They are more limited and again I'd I'd encourage you just to take a look at some of the precedents from.
IDH programs for three programs about sort of how many patients you need and what what level of activity was sufficient for them to get.
Approved.
Great. Thank you and good luck for the rest of year.
Briggs Morrison: Great, thank you, and good luck for the rest of the year.
Great. Thank you.
Briggs Morrison: Alright, thank you.
I am showing no further questions at this time I would now like to turn the conference back to Dr. Morrison.
Operator: I am showing no further questions at this time. I would now like to turn the conference back to Dr. Morrison.
Right. Thank you very much everybody for participating on the call today and for your questions and we look forward to seeing you. All after you hopefully get a little bit of relaxation in August we'll see you in September .
Briggs Morrison: Thank you very much, everybody, for participating in the call today and for your questions. And we look forward to seeing you all after you hopefully get a little bit of relaxation in August. We'll see you in September.
Ladies and gentlemen. This concludes today's conference. Thank you for your participation and have a wonderful day you may all disconnect.
Operator: Ladies and gentlemen, this concludes today's conference. Thank you for your participation and have a wonderful day. You may all disconnect.
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