Tyme Technologies, Inc.
Q2 2020 Earnings Call Transcript

Published: 5 Nov 2019

[Operator:]

Greetings, and welcome to the Tyme Technologies Second Quarter 2020 Earnings Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions]. As a reminder, this conference is being recorded.I would now like to turn the conference over to your host, Mr. Brian Gill of Corporate Communications and Investor Relations for Tyme Technologies. Thank you. Mr. Gill, you may begin.

[Brian Gill:]

Thanks, Tim, and welcome everyone to our second quarter fiscal 2020 investor conference call. The press release reporting on our business updates and financial and operating results can be accessed by going to the Investor Relations section of the corporate Web site at www.tymeinc.com.Joining me today with prepared remarks are Chairman and Chief Executive Officer, Steve Hoffman; our President and Chief Financial Officer, Ben Taylor; our Chief Operating officer, Michele Korfin; our Chief Medical Officer, Dr. Giuseppe Del Priore; and our Chief Business Officer, Dr. Jonathan Eckard.As a reminder, during today’s call we will be making forward-looking statements regarding to our financial and operational outlook in addition to regulatory and product development plans. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.A description of these risks can be found in our most recent 10-Q on file with the SEC. These statements speak only as of today’s date and we specifically disclaim any obligation to update or revise them.I’d now like to turn the call over to our Chairman and Chief Executive Officer, Steve Hoffman.

[Steve Hoffman:]

Thank you, Brian. Good everyone, everyone, and thanks for joining us today. Those who have been following our progress know that Tyme has reached the transformative point in our history. We are now ready for enrollment of two trials designed to be pivotal studying SM-88 for the treatment of pancreatic cancer.It goes without saying that we believe these milestones for Tyme will bring potential, tremendous value and create value in the company going forward. We believe that the encouraging efficacy and safety data that has brought us to this point increases our prospects for success where many before have failed.Furthermore, key opinion leaders in instrumental advisory groups have told us that they share our optimism. Key opinion leaders and oncologists in both the pancreatic and prostate communities have expressed their enthusiasm for SM-88 driven by the compelling data presented at major international medical meetings. Those guys have led to a series of constructive interactions with the FDA, which has resulted in Tyme’s pivotal study protocol having central IRB approval.We are now ready to enroll patients and expect to have Tyme’s pivotal trial data as soon as 2021. Moreover, as you hear this morning, we are also advancing our plans in sarcomas, prostate, breast and hematology. In fact, we are delighted to have renowned hematologist Dr. Susan O’Brien as the newest addition to our Medical Advisory Board.Our cancer metabolism-based therapies have demonstrated activity across a broad spectrum of cancers. We expect 2020 to be marked by the release of more preclinical SM-88 data other clinical and regulatory developments. Importantly, we expect to have access to adequate resources to enable us to advance our pivotal trials and other key initiatives.With that, now I’d like to turn the call over to our leadership team to share with you in more detail their perspectives on the points I just outlined.

[Michele Korfin:]

Thank you, Steve. We are truly excited about the launch of pivotal trials in pancreatic cancer using SM-88. Importantly, as mentioned, we have received IRB or central Institutional Review Board clearance and we are ready to start enrolling patients this quarter.Before I discuss our regulatory focus, I wanted to provide a brief summary on key aspects of SM-88 and the clinical results that have brought us to this critical point in our company’s history.Cancer cells, unlike most healthy cells, need to take in non-essential amino acids such as tyrosine. SM-88 is an oral, modified dysfunctional tyrosine. The cancer cells sees SM-88 and takes it into the cell. SM-88 is then hypothesized to disrupt protein synthesis leading to cell death.SM-88 is our lead investigational therapy in the Tyme cancer metabolism-based therapies or CMBTs platform. SM-88 has demonstrated encouraging efficacy and a well-tolerated safety profile in 15 different tumor types comprising almost 180 patients across four separate studies.These encouraging data include patients treated with both solid tumors and hematologic malignancies. Based on these results, Tyme initiated Phase II trials in pancreatic cancer, prostate cancer and sarcoma.For pancreatic cancer, Tyme conducted a multi-center, open label, dose optimization, randomized Phase II trial evaluating SM-88 in advanced pancreatic cancer. This study, TYME-88-Panc included and actually required patients to have radiographically progressing pancreatic cancer.This was a patient population with a very aggressive cancer. Over 80% of the patients in this study were third-line plus or patients with an extremely poor prognosis. There were about 50,000 cases of advanced pancreatic cancer annually in the U.S. alone. For third-line treatment, there are over 10,000 patients with pancreatic cancer in the U.S. who are actively seeing therapy.There were no FDA approved medicines for this patient population and no ASCO or NCCN guideline recommendations for active therapies. Unfortunately, for these patients, based on published literature, the expected survival for a third-line patient is only two to two and a half months.I can’t emphasize enough the need for better, safer medicines for these patients who have a very poor prognosis. This first part of the TYME-88-Panc study is fully enrolled and still has patients on study. We expect to present the final data in publication and/or presentation in 2020.Based on the encouraging clinical data presented at multiple medical meetings in the second quarter, Tyme has launched its own pivotal trial evaluating SM-88 as a potential therapy for patients with third-line pancreatic cancer.Enrollment is expected to begin this quarter and we expect to have full enrollment by fourth quarter of calendar year 2020. This brings us one step closer to the potential commercialization of our lead CMBT candidate SM-88. We anticipate having data from this pivotal study in 2021.We have had very productive discussions with the FDA and have incorporated their guidance into the pivotal study design. We believe we have a path to approval with this study. There are no current treatments for these patients seeking third-line treatments.Members of our team have broad experience and expertise and launching multiple disease altering cancer therapies into the U.S. market and we are confident that we will be ready to commercialize SM-88 upon successful completion of the trial.In addition, working in close partnership with the Pancreatic Cancer Action Network, we remain on track to open the first trial site in the Precision Promise study by the end of this year. This trial is designed to be pivotal. SM-88 is the first experimental therapy in this adaptive design trial and will be studied in second line pancreatic cancer patients as a monotherapy.For those of you who are not familiar with PanCAN, I encourage you to learn about this exceptional organization. It is the world’s largest advocacy group focused on pancreatic cancer and we are honored that SM-88 was chosen as the first therapy to be examined in its upcoming second line trial. As you can see on the slide, the trial will be conducted at highly regarded institutions around the country.Sarcoma also represents a great unmet medical need. There are approximately 12,000 patients diagnosed each year without good treatment options. Ewing’s sarcoma, one of our treatment arms, often afflicts teenagers and young adults. We are passionate about advancing SM-88 through our trial partnership with Dr. Chawla and the Joseph Ahmed Foundation. The protocol is IRB approved and the trial is also expected to start enrolling this quarter.Now, I will turn the call over to Dr. Giuseppe Del Priore who will share his perspective on the clinical data that he has presented at multiple medical meetings in the second quarter as well as the positive reception he has received from key opinion leaders in both pancreatic and prostate cancers.

[Giuseppe Del Priore:]

Thank you, Michele. I’m very excited to be back from ESMO, a leading international venue for innovative reports. I’d like to share with you the enthusiasm that I experienced from oncologists the world over regarding the TYME-88-Panc study. I want to start by emphasizing the nearly unprecedented core prognosis of these patients at the start of the trial.This is evidenced by our demographic table in the poster and the permissive enrollment criteria that allowed actively progressing patients with no restrictions on tumor size, number of metastases or tumor locations and the ECOG performance status of two. Despite this, we were able to leverage the specificity predicted by the mechanism of action into a tolerable regimen even for these frail, heavily pretreated patients.On Slide 13, we can see that the preliminary median Kaplan-Meier derived overall survival for the evaluable population was approximately 6.4 months as of the spring abstract submission deadline. For comparison, Manax et al reported at ASCO GI in 2019 an expected survival for patients on their third line of chemotherapy as being only two to two and a half months in a similar patient group. Of course, we are continuing to analyze the data to define subsets with better responses from SM-88 to identify patients who appear to experience a more robust clinical benefit than others.We saw the beginning of these efforts come to fruition with the association of CTCs percent reduction and overall survival as shown on Slide 14. Here, patients had at least an 80% CTC reduction trended towards greater survival with a 60% reduction in the risk of death and a hazard ratio of 0.4. Overall, about half of patients achieved at least an 80% reduction in CTC burden, all of which is consistent with our hypothesized mechanism of action and we believe contributes to the improved overall survival seen with disease control.We have further observed, as shown here on the right-side of Slide 15, in a second Kaplan-Meier curve that now also shows a survival trend for patients with PERCIST or PET-based response, which the audience will recognize as a surrogate related to tumor metabolism.To summarize, Slide 15 shows the clinical benefit rate which was reported at ESMO as 44% or experienced by 11 out of 25 evaluable patients based on achieving stable disease or partial response. It is important to note that responses are rate in late-line pancreas cancer trials and do not necessarily correlate with survival, so we are especially excited that many of our patients achieved stable disease and that was associated with longer survival by both RECIST and PERCIST evaluations with patients demonstrating a 72% and 92% reduction in death prospective.On the next slide, 16, we have additional ESMO data that shows that 94.4% of patients remained within 10% of their baseline weight and 38.9% of patients actually gained weight after one cycle of SM-88. Of course, weight loss is a prominent feature of many terminal cancers and perhaps even more so in pancreatic cancer. So clinicians at ESMO told us they were and we believe patients with advanced pancreatic cancer will be encouraged to see this clinically meaningful observation.Interestingly, we saw a hint of this in the data we presented at AACR PANC in Boston where we reported a related trend in leptin levels among patients according to their CTC results. Also from that Boston AACR meeting, this slide, 17, shows that steady state levels of the D-metyrosine AUC 06 were correlated with changes in CTCs from baseline to nadir with slightly stronger correlations for the D-metyrosine versus the L-form.Also at AACR, we reported that certain baseline tumor characteristics, namely the radiomics of the largest metastases correlated with CTC response and survival giving evidence to the efficacy of SM-88. All this was achieved remarkably in a frail, extremely poor prognosis group that typically is not able to receive any additional therapy.On Slide 18, we summarize the safety of SM-88. SM-88 was well tolerated with only 4% of patients or 2 out of 49 reporting serious adverse events deemed at least potentially related to the drug. SM-88 has demonstrated an encouraging safety profile in 15 different tumor types, including solid tumors and hematologic malignancies across four separate studies in approximately 180 patients.Given that there are no effective options to treat this patient population, we have launched our SM-88 pivotal trial in pancreatic cancer and expect to begin enrolling patients in the fourth quarter of this year.Lastly, on Slide 19 and 20, also from ESMO poster presentations, we show the recently completed trial of SM-88 in PSA-recurrent prostate cancer. Favorable changes in PSA kinetics were documented in patients without declines in serum testosterone levels. In fact, higher testosterone was not associated with the worst outcomes.The median duration on therapy was 6.5 months but the range was 2.6 to 14 months. Improvement in CTC numbers were demonstrated and no patient in the trial developed metastatic disease. Adverse events in this population were minimum. The majority were Grade 1 markedly different from standard ADT.Patients reported overall healthy, overall quality of life and sexual activity were largely unchanged from our treatment. Based on these findings, we believe that SM-88 may provide disease control without the side effects associated with standard hormonal therapy and therefore delay the need for ADT or other systemic therapies.These results suggest the clinically meaningful prolongation of the castrate free interval is possible in prostate cancer patients with rising PSA. We are most proud of the association with the leading institutions and investigators in this field, including Memorial Sloan-Kettering, the University of California San Francisco and the Albert Einstein College of Medicine.Prospective trials to confirm SM-88 results are being planned at these institutions without side financing. We are increasingly encouraged that SM-88 has the potential to fill the existing gaps in the unmet medical need of patients and offer a new treatment option for late-stage pancreatic cancer patients and others.Now, let me turn the call over to Dr. Jonathan Eckard, our Chief Business Officer, for this preliminary analysis of the preclinical data on SM-88 and TYME-18.

[Jonathan Eckard:]

Thank you, Giuseppe. Over the past quarter we have been actively advancing our preclinical efforts around SM-88 and our pipeline candidates. As we mentioned earlier this year, we have observed monotherapy anti-cancer activity of SM-88 from in-vitro and in-vivo cancer models.Our ongoing work is aimed at clarifying the cellular, tumor and systemic mechanisms behind SM-88 as well as exploring a range of combinations that can inform us about how to optimally advance SM-88 in a range of cancer settings.In the last quarter, we broadened our academic preclinical collaborations by establishing a research agreement with NYU Langone Medical Center. This collaboration is being led by Dr. Diane Simeone who is the Director of the Pancreatic Cancer Center and associate director of translational research at Perlmutter Cancer Center.This broad collaboration aims to explore the mechanisms of SM-88 in novel animal models, human organoids as well as potential immunological and metabolomic effects of the therapy. This should build upon the work being done at the Mayo Clinic by Dr. Martin Fernandez-Zapico. We anticipate sharing additional preclinical data related to SM-88 around the end of this year and plan to present more data at a major scientific meeting in 2020.Moving on to Slide 23 and TYME-18. TYME-18 is an intra-tumoral administered candidate we announced earlier this year. Like SM-88, the concept behind TYME-18 was to leverage the unique metabolism of the cancer to create a treatment for inoperable tumors to reduce or eliminate these lesions without causing damage to the local tissue.Components of TYME-18 are completely different than that of SM-88 and are designed to leverage the acidic tumor microenvironment and sensitivity of the cancer to certain signaling pathways. Unlike intra-tumoral chemotherapy, we believe the components of TYME-18 are not toxic to the normal tissues and can reduce local and systemic adverse events. This safety profile hypothesis was initially supported by our animal studies.Early in the year, we announced encouraging initial in-vivo xenograft results of tumors treated with TYME-18. In this study, 11 out of 12 mice with TYME-18 treated tumors had this target lesions completed resolved compared to intra-tumoral sham injections in 12 mice where tumors continued to grow aggressively.On Slide 23, there’s a plot of tumor changes from a subsequent TYME-18 study confirming similar target tumor reductions. We continue our TYME-18 preclinical studies with a goal of advancing the program to be IND ready during 2020. At that point we will assess the most strategic options to advance the TYME-18 program into the clinical stage.So now let me turn the call over to Ben Taylor for his comments on our financial and operating results.

[Ben Taylor:]

Thank you, John. As of September 30, 2019, the end of our second quarter for fiscal year 2020, Tyme had 15.3 million in cash and cash equivalents compared to 19.5 million as of June 30, 2019. Our operational cash burn rate for the second quarter of fiscal year 2020 was 4.2 million compared to 4.7 million for the second quarter of fiscal year 2019 and 6.2 million for the first quarter of fiscal year 2020. The decreased cash burn in the second quarter was mainly attributable to the timing of expenditures related to the first part of our TYME-88-Panc trial and our recently completed Phase II prostate clinical trial.We believe that our cash and cash equivalents as of September 30, together with our expected access to additional capital resources, are adequate to fund the discussed trials in pancreatic cancer and sarcoma as well as continue our preclinical and mechanism data. Based on current plans, we project cash operating expenses to average between 5 million and 6 million per quarter for fiscal year 2020.We will continue to identify capital resources across multiple channels, including private, public and strategic markets to support our long-term goals and objectives. I would also continue to expect us to pursue creative ways to advance the pipeline in new areas, including breast, prostate and blood cancers.At this time, I’ll turn the call back over to our Chairman and Chief Executive Officer, Steve Hoffman, for closing comments.

[Steve Hoffman:]

Thank you, Ben. On a personal note, I am very proud of all that we have been able to accomplish in a relatively short period of time and we are really just getting started. We could not have gotten this far without an accomplished team we have in place and I thank each of them for their unwavering dedication towards advancing potentially life-changing therapies to people who are in need.We have quickly evolved our science from the conceptual towards practical application as we begin enrollment of patients in our SM-88 pivotal trials in the fourth quarter of this year. We continue to embark on new opportunities and build the model for sustainable growth by expanding our pipeline and broadening our clinical and regulatory plans.We understand the importance of our work for those in need and we expect 2020 to be a year for good progress to that end. As you have heard today, the company is on a path towards offering novel approach for how difficult to treat cancers are combated in the future. We look forward with great enthusiasm to executing on our strategy for all of our stakeholders in 2020 and beyond, and I thank you for your interest in Tyme.That concludes my prepared remarks. I would now like to turn the call over to the operator for a question-and-answer session.

[Operator:]

Thank you. At this time, we will be conducting a question-and-answer session. [Operator Instructions]. Our first question comes from the line of Swayampakula Ramakanth of Southside Bank [ph]. Please proceed with your question.

[Swayampakula Ramakanth:]

This is RK from H.C. Wainwright. My first question is regarding the TYME-88-Panc Phase III trial in the third-line setting. Could you discuss a little bit about the design and also is there an interim analysis in that study?

[Michele Korfin:]

Hi, RK. This is Michele. Thank you very much for the question. So in regard – there were two questions. Let me touch on the first one around design and then the second one around interim. So first off in terms of design, so this will be our study focused on patients who are third line; so two prior lines of therapy, so third line. It’s a one-to-one randomization between SM-88 and the control arm. The control arm is investigator’s choice.The reason for investigator choice is the control arm is with no FDA approved therapy, no ASCO or NCCN therapy, both our Medical Advisory Board and the FDA agreed that the most appropriate and really the only appropriate control arm would be an investigator choice. So investigators will have a choice of a few single agents for them to choose from for the control arm. The primary endpoint of the study will be overall survival and we anticipate approximately 125 patients in each arm.And then in regards to the interim analysis, we do have a straightforward statistical plan we have discussed with the FDA and our Medical Advisory Board that would be appropriate for a trial of this nature. In addition, we will have the DSMB providing appropriate oversight and guidance as this study progresses.

[Swayampakula Ramakanth:]

Thank you. And then when PanCAN initiates their second-line study, how much of an access would you have for the data that they would generate? And I’m just trying to understand when should we expect the final data from that study?

[Michele Korfin:]

So, RK, great question. And as we mentioned, we anticipate the first site to start up for Precision Promise by the end of this year, so in fourth quarter. That is a blinded study. So we would not have access to data until the study is deemed to be complete.

[Swayampakula Ramakanth:]

Okay. Perfect. My last question is now that you have a renowned Heme/Onc doctor on the Medical Advisory Board, should we expect Tyme to kind of look into certain indications in the Heme/Onc area?

[Giuseppe Del Priore:]

Well, RK, this is Giuseppe Del Priore, the CMO, and of course there are characteristics that would indicate potential efficacy, circulating tumor cells, the various LAT receptors, possible epithelial-mesenchymal transformations that circulating tumor cells share with leukemic cells. So we’ve demonstrated activity and safety in 15 different types of tumor across four cohorts. I would expect that we would see the same in heme malignancies and certainly we really appreciate Dr. O’Brien guidance on that kind of question.

[Swayampakula Ramakanth:]

Thank you.

[Operator:]

[Operator Instructions]. At this time, we have no further questions over the audio portion of the conference. I would like to turn the conference back over to management for closing remarks.

[Steve Hoffman:]

Thank you, Tim, and thank you everybody for your interest and continued support of Tyme. As we had shared with you during our conference call, we have a lot of catalysts and milestones to look forward to in 2020 and we certainly will look forward to sharing that information in 2020. Take care.

[Operator:]

This concludes today’s conference. Thank you for your participation. You may disconnect your lines at this time. Have a wonderful rest of your day.