Tyme Technologies Inc (TYME) 2019 Q4 法說會逐字稿

Good morning, and welcome to Tyme's Fourth Quarter Fiscal 2019 Conference Call. I would like to remind you this call is being recorded. (Operator Instructions)

I would now like to turn the call over to [Brian Gill], Corporate Communications and Investor Relations for Tyme. Thank you. You may begin.

Thank you, operator. And welcome everyone to our fourth quarter and fiscal year 2019 Conference Call. The press release reporting our operating and financial results in addition to the presentation pertaining this webcast can be accessed by going to the Investor Relations section of the corporate website at www.tymeinc.com.

Joining me today with prepared remarks are Steve Hoffman, our Chief Executive Officer; Ben Taylor, our President and Chief Financial Officer; Michele Korfin, our Chief Operating Officer; and our Chief Medical Officer, Dr. Giuseppe Del Priore; and our Chief Business Officer, Jonathan Eckard.

As a reminder, during today's call, we will be making forward-looking statements regarding 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 obligations to update or revise them.

I'd now like to turn the call over to our Chief Executive Officer, Steve Hoffman.

Thank you, [Brian]. Good morning, everybody, and thanks for joining us. I'd like to start today's call by sharing my perspective on 3 key points I am often asked about: The first is our ongoing success in clinical trials; the second is our encouraging new data from recent preclinical findings; and the third is our financial health.

First, today we announce top line data from our ongoing TYME-88-Panc Phase II study, which continues to demonstrate encouraging overall survival in patients with advanced pancreatic cancer.

Preliminary results from Part 1 of the 88-PANC, using information available as of April 25, 2019, demonstrated the following: first, overall survival of our valuable patients is trending to be approximately double the reported survival of this patient population; second, from patients originally reported ASCO GI, 32% were still alive at 6 months or longer; third, remarkably one of earlier patients has just achieved over a year of survival; and fourth, in addition, we learned that circulating tumor cells response correlate with longer survival. Circulating tumor cells have been correlated to prognosis and progression in other types of cancers. So it is not surprising to see it as a good indicator in pancreatic as well. These findings are significant and robust. And it is our plan to do everything in our power to optimize this data to benefit our pivotal trial and increase the prospects of successful NDA filing with the FDA.

The second point is recent preclinical data and SM-88 validates the general safety and power ability of our cancer metabolism-based platform and reinforces our confidence in our ongoing trial in prostate, sarcoma and of course, our planned initiation for pivotal trial for patients with third-line pancreatic cancer. This data demonstrates that SM-88 clearly works as a single agent, demonstrating substantial inhibition of tumor growth.

Moreover, results in this study will support our regulatory efforts, our future product development and continue to expand our strong patent portfolio. And as of April 2, 2019, Tyme had approximately $25.5 million in cash and cash equivalents. This cash position ensures that our pivotal study in third-line pancreatic cancer, patients can proceed as planned, and we expect the pivotal Part 2 of the 88-PANC to initiate in third quarter of 2019 and complete enrollment before the end of 2020. Every day, all of us at Tyme are working on multiply the value we can create for all stakeholders to transformational research in drug development. And our passion to help cancer patients live longer better lives through better safer medicines worldwide.

To begin the discussion of our 2019 results, I'd like to turn the call over to Michele Korfin and thank everybody for their interest in Tyme. Michele?

Thank you, Steve. Our focus at Tyme is developing our cancer metabolism-based therapies to provide new treatment options for patients with unmet medical needs. SM-88 has demonstrated encouraging efficacy across 15 different tumor types, including both solid tumors and hematological malignancies. SM-88 also has demonstrated a well-tolerated safety profile. And our recently published first-in-human study, we reported a median overall survival of almost 30 months amongst 30 patients who were treated with our oral SM-88. These patients in the study all had actively progressing metastatic cancers.

Based on these encouraging results, we initiated our Phase II pancreatic study. Pancreatic cancer is such a challenging diagnosis. Approximately 80% of patients will unfortunately pass away within the first year of diagnosis and the estimated 5-year survival for metastatic patients is only about 3%. Based on our initial data that we presented at ASCO GI, Tyme had a very informative Type C Meeting with the FDA, we will now be amending our Phase II trial to be a pivotal study focused on third-line patients.

Over 10,000 patients with pancreatic cancer in the U.S. reached third line. They are not only no-FDA approved therapies for these patients, but also no ASCO or NCCN recommended therapies. These patients need treatment options. We are encouraged by the initial data we have seen with SM-88 and advanced pancreatic cancer, and we are committed to our TYME-88-Panc study.

At this time, I would like to turn the call over to Dr. Giuseppe Del Priore, our Chief Medical Officer, who will provide the clinical update.

Thank you, Michele. I would like to emphasize that the patients within Part 1 of 88-PANC are in an almost unprecedented cohort of underrepresented individuals. Rarely are patients like these, allowed into trials without severely restricting the enrollment to an unrealistic healthy representation of the real-life situation reflected by the TYME-88-Panc patients. I know of no other trial where so many consented patients died in the brief screening period before randomization. Despite the obvious difficulties these patients face, enrollment completed ahead of schedule. We are using the results of Part 1 to inform the design of the upcoming pivotal trials that will be randomized and have overall survival as a primary outcome as specified in FDA guidance and reflected in our communications with the agency.

As just stated, enrollment completed ahead of schedule, with 49 patients consented, resulting in 39 evaluable as pre-specified in the protocol. As previously mentioned, overall survival of evaluable patient is trending towards an approximate doubling compared to other reports in similar patient populations. For instance, estimated overall survival was 2 to 2.5 months as presented at ASCO GI in 2019 by (inaudible). Also reported at ASCO GI in 2019, but updated here as of April 25, 9 of 28 patients, or 32%, were still alive at least 6 months or longer, with an early patient still alive 1 year after enrollment. We now have enough data to report that circulating tumor cell response correlate with longer survival. Similarly, women have emerged as a significantly -- as having significantly greater survival. Equally important, we have identified several screening criteria that were associated with rapidly declining prognosis and will be reflected in the design of our third-line pivotal trial.

Once on SM-88, patients tolerated the treatment better than nearly all other therapies I have worked with. The level of safety in this frail group of patients is especially important given the toxicity of other treatments prohibit most options for similar third-line patients. The relative lack of toxicity, we believe, is consistent with the theoretical mechanism of action, which also may be the explanation for the reported lack of cross resistance and broad efficacy across multiple tumor types and spectrum of disease. We will present the details related to these observations at upcoming up academic meetings.

Beyond the encouraging details -- beyond the encouraging updated results in the advanced pancreas cancer, we are also updating the now concluded trial of SM-88 in early PSA recurrent prostate cancer. That trial is now ready to direct hypothesis and future investigations in patients at risk for metastatic disease. You can see in the upper-left figure that remarkably few patients have had any progression on imaging studies. And even more importantly, no patients developed metastasis despite an aggressive PSA doubling time at enrollment.

On the upper right, we show the intriguing universal reduction in circulating tumor cells, which are very significant in prostate cancer and has now been confirmed in 88-PANC. At the bottom of the slide, we again show the continued favorable toxicity profile so important for the treatment of tens of thousands of men facing hormone deprivation and the consequences of testosterone deprivation.

And now I'd like to turn the call back to Michele.

Thank you, Giuseppe. Tyme is proud to partner with the Pancreatic Cancer Action Network or PanCAN, for the innovative Precision Promise adaptive design study. Tyme recently joined PanCAN for a meeting with the FDA to finalize the Precision Promise protocol. The second-line arm will open in the second half of 2019. SM-88 was the first experimental therapy chosen for this second-line arm. There are over 20,000 patients with pancreatic cancer seeking second-line therapy. There have been limited advances for second-line treatments. The most recently approved therapy demonstrated a 6.1 month median overall survival versus 4.2 month median for the control arm. Current second-line therapies are also very challenging from a safety standpoint. We saw encouraging SM-88 data in the second-line patients we've studied and are proud of our partnership with PanCAN to advance care for these patients.

Tyme is also finalizing the protocol with the FDA for the TYME-88-Panc amended study. This is the pivotal path for SM-88 for third line. This will be a study comparing SM-88 versus an active control of physician's choice, with the primary endpoint being overall survival. We received initial feedback from the FDA at our February Type C Meeting. And the FDA confirmed the amended study design, as discussed, could be a registration trial. We look forward to incorporating their feedback into the final protocol.

Another clinical area of focus for Tyme is sarcoma. Sarcomas are an orphan disease with approximately 12,000 new cases annually in the U.S. Ewing's Sarcoma accounts for 30% of bone cancer in children and sadly, the 5-year overall survival rate for metastatic disease is only 30%. We've had 2 Ewing's patients treated in the past with SM-88. One had a complete response and one had a partial response. Based on this initial encouraging data, we will approach the study SM-88 further in sarcoma. We are proud of our partnership with the Joseph Ahmed Foundation and Dr. Sant Chawla to initiate the SM-88 study with the first cohort focused on Ewing sarcoma, with the primary endpoint of this study being overall response.

At Tyme, we are committed to partnering with physicians, patients and their loved ones to advance cancer treatments through next-generation cancer metabolism-based therapies to address unmet needs and help cancer patients live longer, better lives.

Now let me turn the call over to Ben Taylor, our President and CFO, who will provide a financial overview and corporate update.

Thank you, Michele. Total operating cash burn for the fourth quarter of fiscal 2019 was $4.2 million. The quarter was below our guided $5 million quarterly burn primarily due to a $500,000 clinical expense that fell into the first quarter of fiscal 2020. Approximately 60% of our annual operating burn was associated with clinical research and development expenses, reflecting the continued focus of the company on advancing our pipeline. As of April 2, 2019, we had $25.5 million in cash and cash equivalents. Looking forward to fiscal 2020, we expect operational cash burn of approximately $5 million to $6 million per quarter. Historically, approximately 1/3 to 1/2 of our annual operational cash burn has been offset outside of significant financings. We believe that, that is appropriate guidance for fiscal 2020 as well.

Driving SM-88 to commercial availability is the core focus of the company, and SM-88 is currently initiating 2 pivotal studies in pancreatic cancer that represent potentially rapid clinical pathways. Through our 88-PANC clinical investigators and the outstanding network of oncologist from Precision Promise, we continue to hear from the KOL communities that SM-88 meets a critical unmet need in the pancreatic treatment paradigm.

Michele mentioned earlier that 10,000 patients annually seek third-line therapy with no existing standard of care. But over 40,000 patients annually receive first line and 20,000 receive second line, all with limited efficacy and substantial treatment-related toxicity. Pancreatic cancer patients need a better option.

At the same time, SM-88 has shown response in 15 different cancer types, and we want to continue expanding development into new cancer indications. Our Precision Promise and sarcoma program both reflect how we have tried to balance our expanded development with capital efficiency. The Precision Promise trials save more than 1/3 in patient cost compared to Tyme doing a similar study internally. In addition, our partnership with JAF covers a large portion of the cost associated with the sarcoma trial. I would expect us to explore options in breast, prostate, hematology and other areas that would move development for it while also conserving capital.

We focus most of our discussion on SM-88, but it's important to note that we have a pipeline waiting for the right time to move forward. We believe that the results from TYME-18 were so compelling that we needed to continue advancing it towards an IND. TYME-18 is an intra-tumoral injection that leverages the same principles as SM-88, but has a completely different chemical composition. Ideally, TYME-18 could be used in connection with SM-88 to provide localized treatment for large or difficult-to-treat tumors while using SM-88 to address the patient's metastatic disease.

In the first half of calendar 2019, we announced initial results on 88-PANC and our Phase II prostate study. We published the first human study in a peer review journal. We made significant progress with the FDA on a path to an NDA, and we launched the sarcoma trial. Looking forward to the second half of 2019, we expect to continue this momentum, including data publications for both Part 1 of 88-PANC and the final results for Phase II prostate studies. Two pivotal trials are expected to initiate in the second half through a Part 2 of 88-PANC and Precision Promise.

We will also be diving into the mechanism of action with results from preclinical in vitro and in vivo work, especially on SM-88 as a single agent in use without the conditioning agents. Lastly, we'll provide an update on TYME-18's pathway for an IND around year-end.

In closing, we are looking forward to a fiscal 2020 as a transformational year for Tyme. That ends our remarks. I would now like to turn the call over to the operator for our Q&A session.

(Operator Instructions)

Our first question is from Sean Lee with H.C. Wainwright.

Looks like we can expect a lot of progress going into the next 12 months. Regarding the upcoming pivotal part -- pivotal study, could you provide us a little bit more color? Maybe the potential sites for the study? What the comparator would be? And what's the dose of SM-88 going to be used?

Yes. So this is Michele, and thank you for the questions. So in regards to the sites and the comparator, so this is an amendment to the TYME-88-Panc study. So the positive news is we will be leveraging the sites -- many of the sites that participated in the Part 1, so that's a positive. And then under the leadership of Giuseppe and Shab from the clinical operations side, we've also had the chance to interact with other sites through the Precision Promise program. So we may look to add on some other sites that we've been interacting with through our medical advisory board. So the positive news is because this is an amendment, we do have the Part 1 sites that would be ready for the amended protocol.

And then in terms of the comparator arm, so it will be a physician's choice. So the physicians will have the option of approximately 3 therapies that they would be using for the third-line patient population. As I mentioned in my prepared remarks, there's unfortunately no FDA-approved therapy, no ASCO- or NCCN-recommended therapy. So based on feedback from the medical advisors and from the FDA, we felt that the physician's choice was the most appropriate comparator. And then in terms of the dose, we will proceed -- be proceeding with the 920-milligram daily dose.

And on the upcoming prostate study data in second half, what's different from the previous updated ASCO GU? What new stuff can we expect?

So this is Dr. Del Priore. I think you'll see an increase in data points, so narrower confidence intervals. I think the message, it was clear. It was pretty dramatic and no metastases, very little progression on any imaging and of course, the circulating tumor cells, which we've now confirmed in 88-PANC. So tighter intervals. I think that's going to lead to some wonderful collaborations and interesting follow-up studies.

Are there any plans right now to move that into a Phase III study as well?

We've had a great deal of interest. You can see it reflected in our pancreas community, but also within the prostate community. And we hope to have some presentations that will add to those plans at upcoming medical meetings.

I see. And my final question is on the newly announced TYME-18 program. Could you provide us with a little bit more color on that one? What it does and when can we see some, maybe, preclinical results from it?

Sean, this is Jon. So we did put on a press release a little while ago, showing that TYME-18 in initial animal genogram models had a dramatic effect on these tumors with about 90% of the tumors completely resolving in the animals. What we would plan on doing is gathering some more details around what is actually occurring and some of the detailed mechanisms around those observations to package them into more of a scientific presentation for appropriate scientific meeting. So as of the guidance, it said, we will be providing updates on what the plans are for that program over the course of this year. And we look forward to providing more details around it at that time.

Our next question is from Arlinda Lee with Canaccord Genuity.

This is Ben Shim on for Arlinda. Impressed on all this progress, looking forward to it towards the second half. My question, I have 2 questions. Can you guys tell us a little bit more about the 1-year survivor in the Part 1 of 88-PANC? And anything that stands out with that patient clinically?

Yes. So this is Dr. Del Priore. As it was reflective of our population, extremely poor prognosis with multiple prior lines. So this person had actually nearly every class that's available within pancreas cancer, plus some investigational agents plus immune oncology therapy. Despite all that, she was able to have the long survival that we are alluded to, and we hope that it will in fact be described in more complete details either at meetings or in additional publications.

Can you hypothesize on what is the distinguishing factor between men and women survival in this disease and treatment?

So just before I answer your question about the gender, I did want to add that the patient with the longest survival is also one of our CTC responders, which we think is extremely important in looking at the SM-88 mechanism of access, CTCs and pancreas cancer and a whole host of other reasons. Now the question of gender is important. It certainly has been looked at extensively in pancreas cancer and in other diseases. So we are extremely encouraged that we've identified a subgroup, and we're searching for the underlying mechanisms. But that implies that there's a biomarker or a genotype that explains as phenotypic difference in outcomes. So I think it's a wonderful endorsement and validation of the mechanism of actions and the benefits of SM-88 in pancreas and in otherwise.

Coming to the circulating tumor cell counts, what is the possibility that potentially being a clinical endpoint given these states of diagnostics today?

Yes. So thank you for the question. So circulating tumor cells have been very important prognostic in a number of different tumor types. We've seen Dr. [Shurin] in prostrate make a comment on that. So I know there's active discussions with the FDA around how to further the use of circulating tumor cells as an important efficacy marker. It was -- it's been very exciting for us to see the data with SM-88 now. We've seen both in our Phase II prostate study and our Phase II pancreatic study, the strong reduction in circulating tumor cells in those 2 different patient populations.

Ladies and gentlemen, we have reached the end of our question-and-answer session. I would like to turn the conference back over to management for closing remarks.

Thank you, operator. We appreciate everybody's attention and interest in Tyme. The management team will be available throughout the course of the day if you have additional questions. And we look forward to sharing with you our achievements and milestones throughout the course of the year. So thanks again and look forward to our next call.

Thank you. This concludes today's conference. You may disconnect your lines at this time. And thank you for your participation.