Q3 2019 Earnings Call

Ladies and gentlemen, thank you for saying Goodbye and welcome to the third quarter 2019.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the third quarter 2019 Kura Oncology earnings conference call. At this time, all participant lines are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star then 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star then zero. I would now like to hand the conference over to your speaker today, Pete Despain, Vice President, Investor Relations at Kura Oncology. Please go ahead. Thank you, Sarah. Good afternoon, and welcome to Kura Oncology's third quarter 2019 conference call. You are joining me on the call.

Her oncology earnings conference call at this time, all participant lines on on listen only mode. After the speakers presentation. There will be a question and answer session to ask the question to one of the session you would need to press Star then one on your telephone.

Please be advised that today's conference is being recorded if you acquire any further assistance. Please press Star then zero I would now like the hand the conference over to your Speaker today, Pete The Spain, Vice President Investor Relations accurate oncology. Please go ahead.

Thank you Sir good afternoon, and welcome to current colleges third quarter 2019 conference call. Joining me on the call from current or Dr. Troy Wilson, Our President and Chief Executive Officer, and Dr., Mark Russell, Our Chief Financial Officer, and Chief Business Officer, Dr., Antonio birth, or Chief Medical Officer, and head of development is also with us and available to answer.

Pete Despain: On call from Kura are Dr. Troy Wilson, our President and Chief Executive Officer, and Dr. Mark Grasso, our Chief Financial Officer and Chief Business Officer. Dr. Antonio Gualberto, our Chief Medical Officer and Head of Development, is also with us and available to answer questions. Before I turn the call over to Dr. Wilson, I would like to remind you that today's call will include forward-looking statements based on current...

A question.

Before I turn the call over Dr. Wilson I would like to remind you that today's call will include forward looking statements based on current expectation.

Pete Despain: Expectation. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause

Such statements represent management's judgment as of today and they involve risks and uncertainties that could cause actual results to differ materially from expected results.

Pete Despain: http://url.curriculum.com Please refer to KURA's filings with the SEC, which are available from the SEC or on the KURA Oncology website, for information concerning risk factors that could affect the company. With that, I'll now turn the call over to Dr. Troy Wilson, President and CEO of KURA.

Please refer to curves filings with the FCC, which are available from the FCC or on the current called your website for information concerning risk factors that could affect the company.

With that I'll now turn the call over there 20, Wilson, President and CEO of grown college.

Troy Edward Wilson: Thank you, Pete, and thank you all for joining us this afternoon. I'd like to start by introducing the two newest members of our senior leadership team, Kathleen Ford, our Chief Operating Officer, and James Basta, our Chief Legal Officer. Kathy joined us in July at a time when strategic prioritization and operational execution became our highest priorities, and she's made an immediate impact. She most recently served at Mercerona, where she led clinical and development operations towards successful drug registrations in both the U.S. and Europe. Jim joined us just yesterday from Biogen, where he spent the past 13 years, most recently as Senior Vice President, Chief Corporation Counsel. He brings a healthy balance of strong business partnering and corporate guardianship, and we're excited to have him on board. Both are welcome additions to our team.

Thank you Pete and thank you all for joining us this afternoon I'd like to start by introducing the two newest members of our senior leadership team Kathleen forward, our Chief operating officer, and James Pasta, Our Chief Legal Officer, Kathy joined US in July at a time, when strategic prioritization and operational execution became.

Highest priorities and she's made an immediate impact. She most recently served at Merck Sirona, where she led clinical and development operations toward successful drug registrations in both the U.S. and Europe .

Jim joined US just yesterday from Biotrue, where he spent the past 13 years. Most recently as senior Vice President Chief Corporation Council. He brings a healthy balance of strong business partnering and corporate guardianship and we're excited to have them onboard both are welcome additions to our team.

Troy Edward Wilson: Now, let me bring you up to speed on each of our programs, beginning with tipifarnib in HRS mutant solid tumors. Last week, we reported updated data from our ongoing Phase II trial of tipifarnib in H. res. mutant head and neck squamous cell carcinomas at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, or the TRIPLE meeting, in Boston.

Now, let me bring you up to speed on each of our programs beginning with Tipifarnib in a trust mutant solid tumors.

Last week, we reported updated data from our ongoing phase two trial of Tipifarnib in a trust mutant head and neck squamous cell carcinomas at the HCR NCR Your T.C. International conference on molecular targets and cancer therapeutics or the triple meeting in Boston.

Troy Edward Wilson: We were very pleased because the results demonstrate a compelling level of clinical activity for tipifarnib in a difficult-to-treat patient population. They validate our strategy to enrich for clinical activity, and the data strongly support the design of our ongoing AIM-HN registration-directed trial. However, before I discuss the significance of these results in more detail, let me quickly recap the data themselves.

We were very pleased because the results demonstrate a compelling level of clinical activity for tipifarnib in a difficult to treat patient population. They validate our strategy to enrich preclinical activity on the data strongly support the design of our ongoing aim matron registration directed trial.

However, before I discuss the significance of these results in more detail, let me quickly recap the data themselves.

Troy Edward Wilson: As of the October 17, 2019 data cutoff date, a total of 21 HNSCC patients with high H-RAS mutant variant allele frequency were enrolled in the ongoing RUN-HN trial, of whom 18 were valuable for efficacy. Ten of the 18 efficacy-evaluable patients achieved a confirmed partial response for an objective response rate of 56 percent. In addition, eight patients experienced disease stabilization, including two who achieved an unconfirmed PR, one of whom was awaiting a confirmatory response assessment as of the data cutoff date. The median progression-free survival of the 18 evaluable patients treated with tipifarnib was 6.1 months compared to 2.8 months on their last prior therapy, including 8.3 months among patients who achieved a PR on tipifarnib and 4.5 months for those Patients had a median of two prior lines of therapy, ranging from zero to six, with no responses observed on their last prior therapy.

As of the October 17th 2019 data cut off date, a total of 21 each in FCC patients with high H. rest mutant very in a little frequency were enrolled in the ongoing run H. and trial of home 18 were evaluable for efficacy.

10 of the 18 efficacy of valuable patients achieved a confirmed partial response for an objective response rate of 56%.

In addition, eight patients experienced disease stabilization, including two who achieved an unconfirmed PR one of whom was a waiting a confirmatory response assessment as of the data cut off date.

The median progression free survival of the 18, a valuable patients treated with Tipifarnib was 6.1 month compared to 2.8 months on their last prior therapy, including 8.3 months among patients who achieved a PR on tipifarnib and 4.5 months for those patients with stable disease patients had a median of two prior lines.

Therapy, ranging from zero to six with no responses observed on their last prior therapy.

Troy Edward Wilson: As a reminder, the overall response rates for the three therapies currently approved for the treatment of HNSCC in the second line, Pembrolizumab, Nivolumab, and Cetuximab, range from 13 to 16 percent, with progression-free survival of approximately two months. Recall that in our previous update from the RUN-HN trial presented at the European Society for Medical Oncology Conference, or ESMO, in October 2018, the data showed a significant association between tumor atras mutant allele frequency and clinical benefit from tipifarnib. We also reported that although the trial was evaluating starting doses between 600 and 900 mg BID, our retrospective analysis of patients on study revealed that due to interruptions and discontinuations at the higher dose, the median dose for patients at the end of Cycle 1 was approximately 600 mg BID.

As a reminder, the overall response rate for the three therapies currently approved for the treatment of HSBC in the second line Pembrolizumab Nivolumab and so tux mab ranged from 13% to 16% with progression free survival of approximately two months.

Recall that in our previous update from the run a Chen trial presented at the European Society for Medical Oncology conference or ESMO in October 2018, the data showed a significant association between tumor HRS mutant a little frequency and clinical benefit from Tipifarnib.

We also reported that although the trial was evaluating starting doses between 609 hundred milligrams to be I'd.

Our retrospective analysis of patients on study revealed the duty interruptions and Discontinuations at the higher dose the median dose for patients at the end of cycle. One was approximately 600 milligrams to be I'd.

Troy Edward Wilson: Based upon these observations, we introduced two changes into the RUN-HN study. First, we require a minimum HRAF mutant variant allele frequency as an entry criterion for enrollment. And second, we established 600 milligrams BID as the starting dose. Notably, we implemented the same changes to the protocol for our AIM-HN registration-directed trial, which was initiated shortly thereafter in November 2018. Since the ESMO 2018 update a year ago, we prospectively enrolled 10 new patients with high HRAS mutant variant allele frequency in the RUN HN trial. Of the eight efficacy-evaluable patients, three achieved a confirmed PR, five had stable disease, including two patients who achieved an unconfirmed PR, one of whom is pending a confirmatory response assessment. Of the two non-evaluable patients, one discontinued prior to an initial tumor response assessment, and the other was awaiting an initial response assessment as of the data cutoff date.

Based upon these observations we introduced two changes into the run H. and study.

First we require a minimum age breast meat and very in a little frequency as an entry criterion for enrollment and second we established 600 milligrams to be ideas, the starting dose, notably we implemented the same changes to the protocol for our aim h. and registration directed trial, which was which was initiated.

After in November 2018.

Since the ESMO 2018 update a year ago, we prospectively enrolled 10, new patients with high H. rest mutant very in a little frequency in the run H. and trial.

Of the eight efficacy of valuable patients three achieved to confirm PR five had stable disease, including two patients who achieved an unconfirmed PR one of whom is pending a confirmatory response assessment of the two non a valuable patients one discontinued prior to an initial tumor response assessment the other was away.

Waiting an initial response assessment as of the data cut off date.

With regard to dose a total of five efficacy invaluable h. in FCC patients started at the 600 milligram dose in the run nature and trial, all of whom achieved an objective clinical response.

Troy Edward Wilson: With regard to dose, a total of five efficacy-evaluable HNSCC patients started at the 600 milligram dose in the RUN-HN trial, all of whom achieved an objective clinical response. We believe there are three key takeaways from last week's RUN-HN update. Number one, the requirement of a minimum HRAS mutant variant allele frequency suggests an effective means to enrich for clinical activity in patients with HRAS mutant HNSCC. Number two, the 600 milligram BID starting dose appears to be better tolerated in this patient population and sufficient to drive durable anti-tumor activity. And number three, given that the RUN-HN trial is a multi-center study including more than 30 clinical sites around the world, the data reflect valuable real-world experience with tipifarinib in this clinical setting.

We believe that there are three key takeaways from last week's run H. and update.

Number one the requirement of a minimum age rest mutant very in a little frequency suggest an effective means to enrich for clinical activity in patients with a trust mutant HSBC.

Number two the 600 milligram be I'd, starting dose appears to be better tolerated in this patient population and sufficient to drive durable anti tumor activity and number three given that the run nature and trial is a multicenter study, including more than 30 clinical sites around the world the data reflect valuable real world experience.

With Tipifarnib and this clinical setting.

Taken together the results presented at the Triple meeting reinforce our view the tipifarnib can provide meaningful clinical benefit to h. NFCC patients, where they trust mutations and they further increase our confidence in the design outcome and probability of success or they may Chen our registration directed trial of Tipifarnib antitrust mutant H. NFCC.

Troy Edward Wilson: Taken together, the results presented at the triple meeting reinforce our view that tipifarnib can provide meaningful clinical benefit to HNSCC patients with HRAS mutations, and they further increase our confidence in the design, outcome, and probability of success of AMHN, our registration-directed trial of tipifarnib in HRAS mutant HNSCC. AMHN was initiated exactly one year ago and is now open in more than 75 clinical sites in the U.S., The AMHN study is designed to enroll at least 59 valuable HNSCC patients with high HRAS mutant variant allele frequencies who have received prior platinum-based therapy. We continue to believe that the AIM-HN study will take approximately two years for full enrollment.

Okay.

Amy Chen was initiated exactly one year ago and is now open in more than 75 clinical sites in the U.S. Europe and Asia.

The I mentioned study is designed to enroll at least 59 invaluable h. in FCC patients with high H. rest mutant very you know they'll frequency.

Who have received prior platinum based therapy, we continue to believe that the Amy trend study will take approximately two years for full enrollment. However, given the design of the study there is the potential does the primary efficacy endpoint or they may Chen could be met if and when 15 confirmed objective responses are UBS.

Served.

Also it's worth noting that since the introduction of the minimum HRS mute and a little frequency requirement. We continue to find that approximately 5% of the patients we screen meet the h. raspberry into low frequency requirement for enrollment.

Our primary goal for the Tipifarnib program is to generate a data package sufficient to support a first application for marketing approval in a trust me nature in FCC, however, with the compelling signals of activity demonstrated from the Triple meeting data. We're also evaluating how we might pursue opportunities for combination with immune therapy came.

Troy Edward Wilson: However, given the design of the study, there is the potential that the primary efficacy endpoint of AIM-HN could be met if and when 15 confirmed objective responses are observed. Also, it's worth noting that since the introduction of the minimum HRAF mutant allele frequency requirement, we continue to find that approximately five percent of the patients we screen meet the HRAF variant allele frequency requirement for enrollment. Our primary goal for the TIPI-FARNIB program is to generate a data package sufficient to support a first application for marketing approval in HRS mutant HNSEC. However, with the compelling signals of activity demonstrated from the triple-meeting data, we're also evaluating how we might pursue opportunities for combination with immune therapy, chemotherapy, and cetuximab in the broader population, including the lower HRS mutant variant allele frequency population.

Oh therapy into tux mab in the broader population, including the lower HRS mutant very into low frequency population.

Given the role of a trust mutations as a mechanism of resistance to standard therapies, we believe tipifarnib could potentially be expanded to 15% to 20% of the h. in FCC population, a meaningful commercial opportunity and one in which today there are no direct competitors to tipifarnib.

Although we believe combinations in earlier lines of therapy, an agent SCC represent immediate opportunities for future label expansion for Tipifarnib. We're also laying the groundwork for expansion to other HRS mutant solid tumor indications.

For example in September we reported that an investigator sponsored phase two trial of Tipifarnib in HRS mutant Urothelial Carcinomas met its primary efficacy endpoint prior to completion of enrollment the trial being conducted at the Samsung Medical Center in Seoul, South Korea further analysis of the trial is ongoing.

Troy Edward Wilson: Given the role of HRAS mutations as a mechanism of resistance to standard therapies, we believe tipifarnib could potentially be expanded to 15 to 20 percent of the HNSCC population, a meaningful commercial opportunity, and one for which there are no direct competitors to tipifarnib. Although we believe combinations and earlier lines of therapy in HNSCC represent immediate opportunities for future label expansion for tipifarnib, we're also laying the groundwork for expansion to other HRES mutant solid tumor indications. For example, in September, we reported that an investigator-sponsored Phase II trial of tipifarniv in atrase mutant urothelial carcinomas met its primary efficacy endpoint prior to completion of enrollment. The trial is being conducted at the Samsung Medical Center in Seoul, South Korea.

And data are expected to be presented at a future medical meeting.

In addition, an investigator sponsored phase two trial of Tipifarnib in lung squamous cell Carcinomas continues to enroll patients the trials being conducted by a lung cancer consortium that consists of more than 150 public and private oncology centers in Spain.

Meanwhile, the discovery of see Axiall 12 pathway Biomarkers offers the potential to expand the opportunity for Tipifarnib well beyond day Trust mutant solid tumors in June we showed the first prospective validation of see Axiall 12 pathway biomarkers to enrich preclinical activity in our ongoing phase two trial of Tipifarnib in Peru.

Referral T cell lymphoma, including a 50% complete response rate and a 100% clinical benefit rate in a subset of heavily pretreated patients with angio immuno plastic T cell lymphoma, or LTL and aggressive form of T cell lymphoma, often characterized by high levels of CX IL 12 expression.

Troy Edward Wilson: Further analysis of the trial is ongoing and data are expected to be presented at a future medical meeting. In addition, an investigator-sponsored Phase II trial of tipifarinib in lung squamous cell carcinomas continues to enroll patients. The trial is being conducted by a lung cancer consortium that consists of more than 150 public and private oncology centers in Spain. Meanwhile, the discovery of CXCL12 pathway biomarkers offers the potential to expand the opportunity for tipifarnib well beyond HRAS mutant solid tumors. In June, we showed the first prospective validation of CXCL12 pathway biomarkers to enrich for clinical activity in our ongoing phase two trial of tipifarnib in peripheral T-cell lymphoma, including a 50% complete response rate and a 100% clinical benefit rate in a subset of heavily pretreated patients with angioimmunoblastic T-cell lymphoma, or AITL, an aggressive form of T-cell lymphoma often characterized by high levels of CXCL12 expression.

We believe the phase two proof of concept data in PTCL AI T. L presented at the European Hematology Association Congress and International Conference on malignant lymphoma earlier this year support multiple registrational opportunities in relapsed refractory lymphoma, and we continue to gather feedback from key opinion leaders.

And regulatory authorities around next steps for this program.

Given the high level of clinical activity observed thus far in the IPO cohort, we continue to enroll patients in that cohort in order to acquire more experience regarding safety and Tolerability in this patient population.

I'm pleased to report that additional data, including new patients from the Hay ITCL cohort have been accepted for an oral presentation by Dr. Thomas with Sig of the Mayo clinic at the upcoming American Society of Hematology annual meeting in December but.

Based on our growing body of data, we believe CX IL 12 pathway Biomarkers may have the potential to unlock the therapeutic value of foreigners will transfer race inhibition across multiple hematologic and solid tumor indications, including diffuse large b cell lymphoma acute myeloid leukemia, cutaneous T cell lymphoma and pancreatic cancer.

Overtime, we believe this could enable registrational strategies for tipifarnib in multiple hematologic and solid tumor indications.

In further support of our development strategy for Tipifarnib I'm pleased to report that the U.S. patent and trademark office recently issued a new patent further extending our exclusivity to the use of any foreign until transfer ace inhibitor for the treatment of CXC, all 12, expressing PTCL or AML. This adds to our growing portfolio of path.

Troy Edward Wilson: We believe the Phase II proof-of-concept data for PTCL-AITL presented at the European Hematology Association Congress and International Conference on Malignant Lymphoma earlier this year support multiple registrational opportunities for PTCL-AITL in relapsed refractory lymphoma, and we continue to gather feedback from key opinion leaders and regulatory authorities around next steps for this program. Given the high level of clinical activity observed thus far in the AITL cohort, we continue to enroll patients in that cohort in order to acquire more experience regarding safety and tolerability in this patient population. I'm pleased to report that additional data, including new patients from the AITL cohort, have been accepted for an oral presentation by Dr. Thomas Witzig of the Mayo Clinic at the upcoming American Society of Hematology annual meeting in December. Based on our growing body of data, we believe CXCL-12 pathway biomarkers may have the potential to unlock the therapeutic value of farnesyl transferase inhibition across multiple hematologic and solid tumor indications, including diffuse large B-cell lymphoma, acute myeloid leukemia, cutaneous T-cell lymphoma, and pancreatic cancer.

Stents involving see Axiall 12 pathway Biomarkers and it follows the issuance of another patent this year directed to a method of treating patients with advanced metastatic relapsed or refractory a trust mutant h. and FCC using any barneveld transfer ace inhibitor.

These new patents expire in 2037, and 2036, respectively. Excluding any possible patent term extension. We believe these new patents strengthen our competitive advantage as we continue to advance the development of Tipifarnib and we intend to continue to aggressively pursue intellectual property protection both in the U.S.

Yes and abroad.

Now, let's spend a moment on each of the emerging pipeline programs, beginning with our erk inhibitor Kale 947.

Kevin on four seven is a potent and selective small molecule inhibitor for which we are advancing its a potential treatment for patients with tumors that have dysregulated activity of the map K pathway.

Our preclinical data suggest accounted for seven has anti tumor activity in K routes or B RAF mutant adenocarcinoma as well as certain subsets of squamous cell carcinoma.

We continue to evaluate dosing regimens for care 947, including a once weekly dosing schedule and a more frequent intermittent schedule with a goal of reaching a recommended phase two dose or maximum tolerated dose by the end of this year or early next year.

We were encouraged to see data from an early stage Erk inhibitor presented at the Triple meeting last week, including single agent responses using a similar weekly dosing schedule with intermittent therapy.

Troy Edward Wilson: Over time, we believe this could enable registrational strategies for tipifarnib in multiple hematologic and solid tumor indications. In further support of our development strategy for tipifarnib, I'm pleased to report that the U.S. Patent and Trademark Office recently issued a new patent further extending our exclusivity to the use of any fornicyltransferase inhibitor for the treatment of CXCL12-expressing PTCL or A This adds to our growing portfolio of patents involving CXCL12 pathway biomarkers, and it follows the issuance of another patent this year directed to a method of treating patients with advanced metastatic relapsed refractory HRS mutant HNSCC using any fornicyltransferase inhibitor. These new patents expire in 2037 and 2036, respectively, excluding any possible patent term extension.

Although most of the patients enrolled in our study today have been in more difficult to treat populations, such as pancreatic and colorectal cancer. The observation of single agent responses from an erk inhibitor support our confidence to move forward with cable 947, we continue to believe our phase one strategy will provide a solid foundation to make data driven decisions.

On the path forward for Kevin on for seven.

Our other emerging pipeline program is scale by 39, a potent selective small molecule inhibitor of the men mixed lineage leukemia or men and MLL protein protein interaction our preclinical data for Kale 539 support the potential for potent anti tumor activity in multiple genetically defined subsets such as tumors with MLL.

All fusions or re arrangements as well as NPM one mutations in September we dose the first patient in our phase one clinical trial of Kale 539 in patients with relapsed or refractory acute myeloid leukemia, giving us our third wholly owned clinical stage oncology assets. The phase one open label dose escalation.

Troy Edward Wilson: We believe these new patents strengthen our competitive advantage as we continue to advance the development of tippi fornib, and we intend to continue to aggressively pursue intellectual property protection both in the U.S. and abroad. Now, let's spend a moment on each of the emerging pipeline programs, beginning with our ERK inhibitor, K0947. KO-947 is a potent and selective small molecule inhibitor of ERK, which we're advancing as a potential treatment for patients with tumors that have dysregulated activity of the MAPK pathway. Our preclinical data suggest that KO947 has anti-tumor activity in KRAS or BRAF mutant adenocarcinomas, as well as certain subsets of squamous cell carcinomas. We continue to evaluate dosing regimens for KO-947, including a once-weekly dosing schedule and a more frequent intermittent schedule, with a goal of reaching a recommended phase 2 dose or maximum tolerated dose by the end of this year or early next year.

In study is designed to determine the maximum tolerated dose of scale 539, which will be administered as a once daily oral dose in 28 continuous day cycles. Upon completion of the dose escalation portion of the trial expansion cohorts or plan to assess the safety and activity of Kao 539 in spin.

Civic genetic sub groups such as NPM one mute.

We believe Kale 539 represents a differentiated approach to the treatment of patients where they ml and we look forward to sharing further updates with you.

With that I'll now turn the call over to Mark for a discussion of our financial results for the third quarter of 2019. Thank you Troy good afternoon, everyone.

Ill provide a brief overview of our financial results here on the call and invite you to review our 10-Q filed today for more detailed discussion.

Research and development expenses for the third quarter, 2019 were 12, and a half million dollars compared to $11.7 million for the third quarter 2018.

The increase in R&D expenses for the quarter was primarily due to an increase in clinical development activities related to our registration directed trial for Tipifarnib.

General and administrative expenses for the third quarter, 2019 were $5.1 million compared to $4.3 million for the third quarter 2018.

The increase in GNS expenses was primarily due to increases in personnel costs and noncash share based compensation.

Net loss for the third quarter of 2019 was $16.4 million or 36 cents per share compared to $15 million or 40 cents per share for the third quarter 2018.

Troy Edward Wilson: We were encouraged to see data from an early-stage ERK inhibitor presented at the TRIPLE meeting last week, including single-agent responses using a similar weekly dosing schedule with intermittent therapy. Although most of the patients enrolled in our study today have been in more difficult-to-treat populations, such as pancreatic and colorectal cancer, the observation of single-agent responses from an ERK inhibitor supports our confidence to move forward with We continue to believe our Phase I strategy will provide a solid foundation to make data-driven decisions on the path forward for K0947.

As of September Thirtyth, 2019, we had cash cash equivalents and short term investments of $250.1 million compared with $179 million as of December 30, Onest 2018.

Based on our current plans, we continue to believe that our existing cash cash equivalents and short term investments will be sufficient to enable us to fund our operating expenses and capital expenditure requirements ended the second half of 2021 with that I'll now turn the call back over to Troy.

Thank you Mark before we jump into Q in a I'd like to take this opportunity to welcome Diane parks the newest member of our board of directors.

Ian is held senior commercial roles at leading companies, including genetic Pharmacyclics, Amgen and kite and she brings valuable experience to our board as we continue to execute on the initial registration directed trial of Tipifarnib and we begin to focus on commercial readiness with that operator, we're now ready for questions.

Mark Grasso: Our other emerging pipeline program is KO539, a potent selective small molecule inhibitor of the Menin Mixed Lineage Leukemia, or Menin-MLL, protein-protein interaction. Our preclinical data for KO539 support the potential for potent anti-tumor activity in multiple genetically defined subsets, such as tumors with MLL fusions or rearrangements, as well as NPM1 mutations. In September, we dosed the first patient in our Phase 1 clinical trial of KO539 in patients with relapsed or refractory acute myeloid leukemia, giving us our third wholly-owned clinical stage oncology assay. The Phase I Open Label Dose Escalation Study is designed to determine the maximum tolerated dose of KO539, which will be administered as a once-daily oral dose in 28 continuous Upon completion of the dose escalation portion of the trial, expansion cohorts are planned to assess the safety and activity of KO539 in specific genetic subgroups, such as NPM1 mutants. We believe KL539 represents a differentiated approach to the treatment of patients with AML, and we look forward to sharing further updates with you. With that, I'll now turn the call over to Mark for a discussion of our financial results for the third quarter of 2019. Thank you, Troy.

Thank you.

As a reminder to ask the question you need to press Star then one on your telephone.

Our first question comes from the line of Chris Shibutani with Cowen. Your line is now open.

Hi, everyone. This is Canberra on for Chris.

I have a couple of questions. The first one is in regard to your biomarker strategy. So should we be expecting at ash that you'll be breaking down those T cell responses by cursory mutations or other biomarkers.

Pam Thanks for the question, let me ask Antonio Who's here with Us if he can address your question.

Yes, we we estimate to extend the data that was initially person good that he had the this year.

We have continued growing.

Patients, we we want to so they've got to values.

Good data with Q to city deal tool since you may recall, we swapped to 75% response rate. So so that was quite exciting.

We we are feeling based big 18 to determine whether.

We can sustain these high level of response in the subsidy Q2, you tube audience.

Got it. Thanks, so much and then another logistical question first I guess thanks.

For the Triple meeting data.

Mark Grasso: All right. Good afternoon, everyone.

Mark Grasso: I'll provide a brief overview of our financial results here on the call and invite you to review our 10-Q file today for more detailed discussion. Research and development expenses for the third quarter of 2019 were $12.5 million compared to $11.7 million for the third quarter of 2018. The increase in R&D expenses for the quarter was primarily due to an increase in clinical development activities related to our registration-directed trial for Tiptarnib. General and administrative expenses for the third quarter of 2019 were $5.1 million, compared to $4.3 million for the third quarter of 2018. The increase in G&A expenses was primarily due to increases in personnel costs and non-cash share-based compensation.

Congratulations on that what.

What do you think the enrollment rate.

We will look like compared with.

That trial in the NHL trial.

Sure Pam so.

If you look at Rene Chen NHL and run being the the ongoing phase two trial and aim being the pivotal trial, they're completely different animals right.

Rene Chen is in is in 30 centers, it's been up and running here for a number of years aim is a global registrational directed trial.

We're pleased that were at the point, where you know we have more than 75 sites open.

But but much of the past year has been spent.

Getting sites online getting them activated getting them screening.

And we're really first in class here. So we're learning as we go I think we're very pleased with the data coming out of the Triple meeting update it showed that the the.

Mark Grasso: The net loss for the third quarter of 2019 was $16.4 million, or $0.36 per share, compared to $15 million, or $0.40 per share, for the third quarter of 2018. As of September 30, 2019, we had cash, cash equivalents, and short-term investments of $250.1 million, compared with $179 million as of December 31, 2018. Based on our current plans, we continue to believe that our existing cash, cash equivalents, and short-term investments will be sufficient to enable us to fund our operating expenses and capital expenditure requirements into the second half of 2021. With that, I will now turn the call back over to Troy.

Amendments that we made to the protocol in terms of the varies a little frequency and the 600 milligrams, starting dose where the rate changes and now we're just sort of full on in operational execution of the pivotal and we're still guiding to approximately two years to full enrollment.

So hopefully that addresses your question.

Yes, Thank you sound like.

Sure. Thanks.

Thank you. Our next question comes from the line of Ren Benjamin with JMP Securities. Your line is not open.

Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress.

Troy, maybe just starting off to the just based on your discussions with the regulatory agency I mean, you mentioned that.

Once the first 15 responders or confirmed.

Troy Edward Wilson: Thank you, Mark. Before we jump into Q&A, I'd like to take this opportunity to welcome Diane Parks, the newest member of our Board of Directors. Diane has held senior commercial roles at leading companies, including Genentech, Pharmacyclics, Amgen, and Kite, and she brings valuable experience to our Board as we continue to execute on the initial registration-directed trial of tipifarnib and we begin to focus on commercial readiness. With that, Operator, we're now ready for questions.

You could you could potentially go ahead and filed it I did I hear that correctly is there a minimum duration of response, that's that's necessary for the agency and kind of can you talk to us a little bit since we're getting close to these this event a little bit of a commercial strategy that you plan to unfold about how many.

Salespeople do you think might come into the organization and how you plan on moving forward.

Sure Ren Thanks for the questions, let's start with them.

Operator: Thank you. As a reminder to ask a question, you will need to press star then 1 on your telephone. Our first question comes from the line of Chris Chibutani with Cowen. Your line is now open. Hi everyone, this is Pam Barrett on behalf of Chris.

Let me ask Antonio if he can respond to your question about.

No.

What happens if and when we reach 15 confirmed objective responses.

Yes, so there's no particular requirements by the agents CEO .

Pam Barrett: I have a couple of questions. The first one is in regard to your biomarker strategy. So should we be expecting at ASH that you'll be breaking down those AITL responses by CURS3 mutations or other biomarkers?

Specific to reach more response.

As you can imagine you know once youre comparing the responses.

You will be cycle full cycle six in some cases, so and so you will you already will have seemed responses for fall two to six months.

Troy Edward Wilson: Pam, thanks for the question. Let me ask Antonio, who's here with us, if he can answer your question.

Antonio Gualberto: All right.

Antonio Gualberto: Yes, we are expecting to extend the data that was initially presented at IHA this year. We have continued enrolling AIDL patients. We want to further characterize the data with KIR3DL2. As you may recall, we saw up to 75% response rate, so that was quite exciting. We are further investigating to determine whether we can sustain this high level of response in the subset of KIR3DL2 variants.

So the reminder, the median progression free survival in these cities how about two months. So so that gives you an idea all the Oh, we have shown.

I'm going to come pretty sort of Weibo recently in now what people meet the update those six months. So that you didn't give fuel and the potential well keep you thought I mean these sitting comparative we at this time middle care a US you can imagine this will be part to do that review.

Pam Barrett: Got it. Thanks so much.

Pam Barrett: And then another logistical question. First, I guess, thanks, for the triple meeting data. Congratulations on that. What do you think the enrollment rate will look like compared with that in the AIM-HN trial?

A quick students by Dave theory.

But they say you know pursued this note in particular.

Troy Edward Wilson: Sure, Pam. So if you look at RUN-HN and AIM-HN, RUN being the ongoing Phase II trial, and AIM being the pivotal trial, you know, they're completely different animals, right? RUN-HN is in 30 centers. It's been up and running for a number of years. AIM is a global, registrational-directed trial. You know, we're pleased that we're at the point where, you know, we have more than 75 sites open, but much of the past year has been spent getting sites online, getting them activated, getting them screening, and we're really, you know, first in class here, so we're learning as we go. I think we're very pleased with the data coming out of the triple meeting update. It showed that the amendments that we made to the protocol in terms of the variant allele frequency and the 600 milligram starting dose were the right changes, and now we're just sort of full-on in operational execution of the pivotal, and we're still guiding to, you know, approximately two years to full enrollment, so, you know, hopefully that addresses your question.

Duration wall response requirement for filing in the city.

And ran with respect to this.

Well go ahead I'm sorry go ahead.

I was just mentioning that the remaining of the question regarding the commercial strategy.

Yeah. So so.

No I think as I mentioned were quite encouraged by the data that we presented at the Triple meeting update.

We are.

Beginning the steps for commercial readiness and everything that that entails I think it's early to be giving you guidance on specifics around.

You know when organizational size restructure, but we're certainly.

Working through a lot of those those details in anticipation of what we hope will be positive result for the mentioned trial here and I would expect that as we get further into it will provide you more guidance on on the steps around commercialization. It's just a bit early at this stage a bit premature.

Got it.

And then just you mentioned the combination the potential for combinations and that.

The Triple meeting data really led you to believe this can you maybe highlight what within the data is really leading you to this conclusion. When these combinations studies might in fact to begin.

Pam Barrett: Thank you so much.

Reni John Benjamin: Thanks for watching. Thank you. Our next question comes from the line of Ren Benjamin with JMP Securities. Your line is now open. Hey, good afternoon guys. Thanks for taking the questions and congrats on the progress. Troy, maybe just starting off, just based on your discussions with the regulatory agency, I think you mentioned that once the first 15 responders are confirmed, uh... you know you could you could potentially go ahead and filed a right but i hear that correctly is there a minimum duration of response that's necessary for the agency and and kind of can you talk to us a little bit uh... since we're getting close to these that this event a little bit of a commercial strategy that you plan to unfold about how many salespeople do you think might come into the organization and and how you plan on moving forward

Sure, let again, let me ask Antonio if he can speak to sort of the data and the rationale for the combinations.

You saw us thinking.

You can.

You have seen from the.

The board meeting update.

Patients cutting you asked mutations.

Not really system to this time dental care either Moscone. This kind of middle care will deploy your line will soon be was chemotherapy. If you will see me immune therapy. If you will sit to seamap alone won't we combination. So in other words depressant self said trusts mutation good I see some traditional middle care no way.

Troy Edward Wilson: Sure, Ren, thanks for the questions. Let's start with, let me ask Antonio if he can respond to your question about, you know, what happens if and when we reach 15 confirmed objective responses.

When the two more calories 20 puts in a body in Ireland sequence. Your class all high year, you can see activity. We typically single indeed. The question then remains you know when when the two more.

Antonio Gualberto: Yes, there's no particular requirement by the agency for a specific duration of response. As you can imagine, once you confirm the responses, you will be in cycle 4 or cycle 6 in some cases.

Let's see kind of refinancing so embarrassing when it carry less than 20%. So those sitting you know the the Portugal bitumen, we said last mutation may not be sufficient.

Antonio Gualberto: So you will already have seen responses for 4 to 6 months. As a reminder, the median progression-free survival in this setting is about 2 months. So that gives you an idea of the... We have also shown progression-free survival recently in our triple-mythic update of 6 months. That gives you an idea of the potential of TP farming in this setting compared with the standard of care. As you can imagine, this will be part of the review questions, you know, by the FDA. But this, you know, per se, there's not a particular duration or response requirement, you know, for filing.

Full could be funny to assess the single again, but it could be an opportunity for beside me to the be made the system to this time they don't care. So so the this is not.

So as I guess hypotheticals is essentially it tenancy data.

In the case so his last week, we said to team up so.

Publish.

The so have been probably find great come on co workers that when they assess mutation. These the you know normally those patients you know progress too.

Antonio Gualberto: and Ren, with respect to the Oh, go ahead. I'm sorry. Go ahead.

Antonio Gualberto: I was just mentioning the remaining questions regarding the commercial strategy.

Quickly enroll in India first went to so good opportunity for pp funny to combined with this time middle clear maybe any mutual approach will be those patients we saw a low.

Troy Edward Wilson: Yeah, so, you know, I think, as I mentioned, we're quite encouraged by the data that we presented at the Tribble Meeting update. You know, we are beginning the steps for commercial readiness and everything that that entails. I think it's early to be giving you, you know, guidance on specifics around, you know, an organizational size or structure, but we're certainly working through a lot of those details in anticipation of what we hope will be, you know, a positive result for the AIM-HN trial here. And I would expect that as we get further into it, we'll provide you more guidance on, you know, the steps around commercialization. It's just a bit early at this stage, a bit premature.

Body analytics frequency Oaks is fast, but but obviously you know piece on the will have an opportunity to combined with the tons that okuno eventually the do it on population.

And when do you think you might begin those kinds of exploratory studies.

Well, obviously you know they say, there's a lot that we have done preclinically.

We need to make major decisions. So what will be the potential combination partner. So the cutting to be that that we have you under discussion we within the company with others.

Troy Edward Wilson: Got it. And then you mentioned the combination, the potential for combinations, and that, you know, the triple meeting data really led you to believe this. Can you maybe highlight what within the data is really leading you to this conclusion when these combination studies might actually begin?

Great. Thanks, very much Ranjan my questions Oh, sorry, Thank you Randy.

Well I was just gonna say on that point I mean, I think you know now we see sort of two illustrations of our strategy right. So we as an initial foothold.

Antonio Gualberto: Sure. Again, let me ask Antonio if he can speak to some of the data and the rationale for the combination.

Both where they track so now see Axiall 12 in the context of of T cell lymphoma, we're looking to prioritize those places where we can get accelerated development and ideally approval with a single arm trial, but looking toward with an eye toward you know moving to earlier lines of therapy moving in combination at.

Antonio Gualberto: Yes, so as you have seen from the triple meeting update, the patients carrying SRAS mutations were resistant to the standard of care. It didn't matter if the standard of care or the prior line of therapy was chemotherapy, if it was immune therapy, if it was 2CMAP alone or in combination.

And it's important to note I mean to this point, we don't see any direct competition on either a traps or horsey axiall 12 from pharmacy or other foreigners will transfer ace inhibitors. So antonio's right. We're at a point where weak theres a lot of things, we can do with foreign until transfer rates inhibition, and we want to make sure we prioritize.

Antonio Gualberto: So, in other words, you know, the presence of SRAS mutations drives resistance to the standard of care. Now, when the tumor carries 20% varying allele frequency of SRAS or higher, you can see activity with tpFARNAS as a single agent. The question then remains, you know, when the tumor, let's say, carries 5%, 7%, when it carries less than 20%. So in those settings, the portion of the tumor with the SRAS mutation may not be sufficient for tpFARNAS to act as a single agent, but it could be an opportunity for tpFARNAS to delay resistance to the standard of care. So this is not just hypothetical.

Them and sequence them in the right order and we'll have more we can share with that in the you know in the months to come.

Terrific. Thank you for taking the questions.

Thank you. Our next question comes on line of Jonathan Chang with SVB Leerink. Your line is now open.

Good afternoon. This is John Bair on for Jonathan Thanks for taking my questions.

Okay, and congrats on having the LTL data being selected for an old presentation at ash.

If you could could you help us set investor expectations ahead does.

Antonio Gualberto: There's actually extensive data in the case of SRAS with 2CMAP that have been published. It has also been published by Drake and co-workers that when a SRAS mutation is there, you know, normally those patients progress too quickly, you know, in the first line. So, a good opportunity for tpFARNAS to combine with the standard of care. Maybe an initial approach will be those patients with low varying allele frequency of SRAS, but obviously, you know, tpFARNAS will have an opportunity to combine with the standard of care eventually in the overall population.

T L update in terms of how many more patients and how much more follow up we might expect versus the data we saw yeah.

Sure John Thanks for the question, let me, let Antonio a you know.

Ill answer your question.

Yeah.

I will say that is just incremental so since he or she can you imagine they did the primary endpoint.

All those cohorts you know WASC reach you know we have proof of concept well see me IPO on the PTCL malls, we continue.

Antonio Gualberto: And when do you think you might begin those kinds of exploratory studies?

Obviously, you know we had three even now to the saying all the people. Finally studied the discussions you know we today again Cecil on DC side, but you know we want to continued engagement with investigate on Sunday can become sites. So there's still remains open to two at the beach and are there.

Antonio Gualberto: Well, obviously, you know, there's a lot that we have done preclinically, and, you know, we need to make major decisions about, you know, what could be the potential combination partners. So this is currently what we are currently discussing within the company.

Troy Edward Wilson: That's great. Thanks very much.

Troy Edward Wilson: Oh, sorry. I got it.

Troy Edward Wilson: Well, I was just going to say on that point. I think, you know, now we see sort of two illustrations of our strategy, right? So we, as an initial foothold, both with H-RAS and now CXCL-12 in the context of T-cell lymphoma, are looking to prioritize those places where we can get accelerated development and, ideally, approval with a single-arm trial, but looking with an eye toward, you know, moving to earlier lines of therapy, moving in combination. And it's important to note, I mean, to this point, we don't see any direct competition for either H-RAS or CXCL-12 from other foreign cell transferase inhibitors. So Antonio's right. We're at a point where, you know, there are a lot of things we can do with foreign cell transferase inhibition, and we want to make sure we prioritize them and sequence them in the right order. And we'll have more we can share with you in the, you know, in the months to come.

Thank you as you know something very similar to what we the you know we've we've since class, a but but I understand that we'll be at some point you switch put on the face to face team to readiness for 40 people on the study.

Okay. Thank you and regarding those conversations both internally and with regulators. How are you thinking about a development path forward for AI T L and PTCL broadly and what type of Registrational trials you might run.

Yeah.

So few the mine to try and willingness is so big they are attuned to the fact that the the treatment to be funding with the IPO translate that to Hydratight response rate that opened the opportunity to a potential oxylate. It took a pretty well you know.

Operator: Thank you. Our next question comes from the line of Jonathan Chang with SVB.

Jonathan Chang: Your line is now open. Good afternoon, this is John Barrett on behalf of Jonathan. Thanks for taking my questions. And congrats on having the AITL data selected for an oral presentation at ASH. If you could, could you help us set investor expectations ahead of the AITL update in terms of how many more patients and how much more follow-up we might expect versus the data we saw at EHA?

Typically conditional absolutely depending on the agency those who normally design so thoughts single on single again on.

You know seem to lead to tool was a war.

If it's fast the sighing honest and at the.

In the case, so the rates so that he felt T cell lymphoma, we sort of responses, but we also saw a high grade could be Ccs WPC to die may meet different design, you know Mitt maybe a kind to employing it progression free survival Allison. So so basically what I'm getting too is that it may be a big.

Troy Edward Wilson: Sure. John, thanks for the question. Let me let Antonio, you know, answer your question.

Antonio Gualberto: Yeah, you know, I would say that it's just incremental, so as you can imagine, the primary endpoint of those cohorts, you know, was reached, you know, we have proof-of-concept, both in AITL and the PTCL NOS. We have continued, you know, obviously, you know, we are driven now to the design of a pivotal study, the discussions, you know, with agencies on this design, but, you know, we want to continue the engagement with investigators and the clinical sites, so the study remains open to add additional patients, you know, something very similar to what we did, you know, with CES-RAS, but I understand there will be, at some point, a switch from the phase two testing to readiness for a pivotal study.

Where for a T. I mean like Histologies, a two to four Lloyd a kind of a single arm approach. Their schools you know all did it besides maybe require for other substrates, so pretty could on T cell lymphoma.

Great. Thank you for taking my questions.

Thanks, John .

Thank you. Our next question comes from the line of Tyler Van Buren with Piper Jaffray. Your line is not open.

Hey, guys. Good afternoon, congrats on all the progress with respect to the to before the program.

Clearly, you're seeing great data and great response rates and head and neck and AI TL on on the team sides, but you know in solid you've got.

Antonio Gualberto: Thank you. And regarding those conversations both internally and with regulators, how are you thinking about a development path forward for AITL and PTCL broadly and what type of registrational trials you might run?

To consider whether you move into earlier lines with Cabos and have mek, you've got bladder or potentially long in Haim you have sale 12 positive PTCL know us deal Bcl because a lot of potential indications to go. After so can you just take a step back and help us understand.

Antonio Gualberto: So if you don't mind, Troy, I will address this. So I think the fact that the treatment of TP funding with the AITL translated to a high rate or response rate that opened the opportunity for a potential accelerated approval, you know, you know, typical conditional accelerated, you know, depending on the agency. Those normally have designs of single arm, single agent, and, you know, similarly to what was our SRAS design and strategy. In the case of peripheral T-cell lymphoma, we saw responses, but we also saw a high rate of disease stabilization that may need a different design, you know, maybe a time to end point, progression-free survival, et cetera. So, basically, what I'm getting at is that it may be required for AATL and ATL-like histologists to follow a kind of single-arm approach versus, you know, other designs may be required for other subsets of peripheral T-cell lymphoma.

Beyond these initial two indications, which one or two.

The most interesting to own prioritized in terms of moving until late stage development.

Yeah, a toddler thanks for the question.

And just to to confess it's still a work in progress.

I think we're pleased really with with two things one is the.

The level of activity that we're seeing these biomarker guided subset.

Maybe three things the ability to move from the initial relapsed refractory indications that we can access as a as a small company to potentially larger indications and then third as we as we said in the comments the growing IP estate, that's helping to potentially protect protect the use of not only tipifarnib, but.

To exclude others, who might come along with point of sale transfer Ace inhibitors as.

As Antonio mentioned, we see a clearing compelling opportunity in the head and neck squamous cell carcinoma.

Troy Edward Wilson: Great, thank you for taking my question. Thank you. Our next question comes from the line of Tyler Van Buren with Piper Jeffery.

Space the level of activity that we're seeing in terms of objective responses is is compelling relative to the current standard of care and Theres. Good rationale to believe that you could move that to earlier lines of therapy and with you know with a thoughtful combinations that you could broaden the patient population.

Tyler Van Buren: Your line is now open. Hey guys, good afternoon, congrats on all the progress. With respect to the TIPI-FARNIB program, clearly, you're seeing great data and great response rates in head and neck and AITL on the heme side, but in solid, you've got to consider whether you move into earlier lines with combos in head and neck. You've got bladder, potentially lung. In heme, you have CXCL12 positive, PTCL-NOS, and DLBCL. You guys have a lot of potential indications to go after, so can you just take a step back and help us understand beyond these initial two indications which one or two might be most interesting to you all and prioritize in terms of moving into late-stage development?

Those are studies that would likely need initially phase one combinations and then probably a larger randomized studies. So those are things that we have to obviously think about carefully.

What we would want to take on and the timing, but thats clearly an area that we would prioritize.

T cell lymphoma in AI TL in particular is just again, an example, where tip is the most active agent it gives us a foothold in the heme space.

And it gives us an opportunity as I think you've just articulated whether we do it alone or whether we do it with a partner of being able to you know to more meaningfully address some of these larger population and that that question is very much on our mind in something that you know I think we're going to spend.

Troy Edward Wilson: Yeah, Tyler, thanks for the question. And just to confess, it's still a work in progress. I think we're pleased, really, with two things. One is the level of activity that we're seeing in these biomarker-guided subsets. Maybe three things. The ability to move from the initial relapsed refractory indications that we can access as a small company to potentially larger indications. And then third, as we said in the comments, the growing IP estate that's helping to potentially protect the use of not only tpFARNIB but to exclude others who might come along with farnesyl transferase inhibitors. As Antonio mentioned, we see a clear and compelling opportunity in the head and neck squamous cell carcinoma space.

A considerable amount of time going forward trying to get right.

Do you guys expect to have increased clarity on this bye bye say the first half for middle of next year is is that possible kind of guidance to provide.

Yeah, I mean, I don't I don't know that I'd I understand what's your which where you're coming from we certainly want to be able to provide clarity on next steps, but to the point is some of these studies are you know some of these studies we can take on now some of them are are probably.

Better put off to a point, where we have greater operational and financial resources and that's something we'll have to factor in.

But we we expect to be able to give you you know increasing clarity on the next steps for Tipifarnib NR foreigners will transfer Ace inhibitor franchise as we keep going.

Troy Edward Wilson: The level of activity that we're seeing in terms of objective responses is compelling relative to the current standard of care, and there's good rationale to believe that you could move that to earlier lines of therapy and, with thoughtful combinations, broaden the patient population. Those are studies that would likely need initially phase one combinations and then probably larger randomized studies.

Okay got it and then finally on 539, the Menin MLL inhibitor can you just briefly described the dose escalation scheme and whether you would expect to whether you think theres the potential to see monotherapy activity and if you guys play into.

And particularly in the subgroups of patients for example, the patients with fusions et cetera.

Troy Edward Wilson: So those are things that we have to obviously think about carefully, what we would want to take on, and the timing. But that's clearly an area that we would prioritize. T-cell lymphoma and AITL, in particular, are just, again, an example where TIPI is the most active agent.

Yes so.

Great question RTO, Tyler, let me ask Antonio if he can answer that for you.

Yes, so they'd be saying past its a modified by nation design, but you know at the high level is not very depending on the phase you know three plus city.

Troy Edward Wilson: It gives us a foothold in the heme space, and it gives us an opportunity, as I think you just articulated, whether we do it alone or whether we do it with a partner, to more meaningfully address some of these larger populations. And that question is very much on our mind and something that I think we're going to spend a considerable amount of time going forward trying to get right.

The sign on to you know maybe we have time you need to absolute this phase we are not doing select showing the initial escalations in or would that I agree fit into the being one or the translocation, but you know we reset our opportunity to select patients when would reach the how you to bonuses.

Tyler Van Buren: Do you guys expect to have increased clarity on this by, say, the first half or middle of next year? Is that a possible kind of guidance to provide?

Troy Edward Wilson: Yeah, I mean, I don't, I don't know that I understand what you're saying or where you're coming from. We certainly want to be able to provide clarity on next steps. But to the point, you know, some of these studies are, you know, some of these studies we can take on now; some of them are probably, you know, better put off to a point where we have greater operational and financial resources. And that's something we'll have to factor in. But we, you know, we expect to be able to give you increasing clarity on the next steps for TIPI-Farnab and our farnesyl transferase inhibitor franchise as we keep going.

They've got to you in each acquisti on base from the preclinical data used to some expectation will the old or ability on responses asset single agent.

Just a quick follow up for the patients the genetic subgroups hotel fusions or partial tandem duplications.

Or and PMN, one mutations if you combine those what percentage of the broader population would you say has these.

Genetic classifications.

Tyler Van Buren: Okay, got it. And then finally, on 539, the Menin-MLL inhibitor, can you just briefly describe the dose escalation scheme and whether you would expect to, whether you think there's the potential to see monotherapy activity, and if you guys plan to, you know, and particularly in subgroups of patients, for example, patients with fusions, etc.

So if we received but you know returning to the adult population vehicle pulpwood Polish population.

NPL Juan will be they may go targacept seemingly a waterfall depopulation on.

Regarding the other targets that you mentioned you note that this hockey stick this high level of core mutation. So it's very difficult to to determine what will be a few population will fall off.

Tyler Van Buren: ?

Antonio Gualberto: Great question, Tyler. Let me ask Antonio if he can answer that for you.

Antonio Gualberto: Yes, so the design is a modified variation design, but you know, at the high level, it's not very different from a 3 plus 3 design, you know, maybe with an initial accelerated phase. We are not doing selection in the initial escalation, you know, without referring to NPM1 or the translocation, but you know, we reserve our opportunity to select patients when we reach the higher dose. Regarding your initial question, based on the preclinical data, yes, there is an expectation of the probability of responses as a single agent.

Let's say timing it sent to the big bets sous chef CMP and ones. So most of these patients will have commutations, but we refer to what will be at what made you are targeting MP unwind.

Just base the song all populate the tough from DCD area and the like you said about you potentially according to hold the population.

Tyler Van Buren: Just a quick follow-up, for the patients, the genetic subgroups with MLL fusions or partial tandem duplications or NPM1 mutations, if you combine those, what percentage of the broader population would you say has these genetic classifications?

Okay. Thanks, so much for taking the questions.

If you Tyler.

Thank you. Our next question comes from the line of Joel Beatty, well Citi. Your line is not open.

Hi, Thanks for taking my questions.

Antonio Gualberto: So, if we refer to the adult population, the adult population, NPM1 will be the major target. It's approximately a quarter of the population. And regarding the other targets that you mentioned, the fact is that there's a high level of commutation, so it's very difficult to determine what will be a pure population of, let's say, Tandem FL3 versus just NPM1. So, most of these patients will have mutations, but if we refer to what will be our major target, NPM1, and just base this on public data from TCGA and the like, it's about potentially a quarter of the population.

First one is maybe a follow up to a couple other responses for earlier in the queue in a where it seems like there's a lot that CRE is able to take on right now by itself regarding to your pipeline agents simple going on there's also been other opportunities have been highlighted that may be better handled by a partner sometimes.

Be curious you know just thoughts on.

How to think about it the timeline for partnering is now a potential timeline.

I could be looked at.

Are there additional you know hurdles to get passed before that becomes.

Higher priority.

Yeah, Joe Thanks for the question marks here with me, let me ask him if he can speak to that sure Hey, Joel partnering from our standpoint, you know as as we've articulated in the past.

Tyler Van Buren: Okay, thanks so much for taking the questions. Thank you, Tyler. Thank you. Our next question comes from the line of Joel Beattie with Citi. Your line is now open.

Doing anything that Encumbers rights on Tippi, particularly in the U.S.

Joel Beattie: Hi, thanks for taking the questions. The first one is maybe a follow-up to a couple other responses earlier in the Q&A, where it seems like there's a lot that Cura is able to take on right now by itself regarding your pipeline agents. But then there's also been other opportunities that have been highlighted that may be better handled by a partner. So I'm just curious, just thoughts on how to think about the timeline for partnering is now a potential timeline that could be looked at? Are there additional hurdles to get past before that becomes a higher priority?

The hurdle there is high for us.

And we see a very attractive go it alone strategy, particularly in the initial markets, we're talking about here, including.

Relapsed refractory head and neck and and a RTL.

And I'd be cautious to set any timing or expectations around anything we might do on the strategic partnering front, whether it be on tipifarnib more or any of the pipeline assets.

Got it. Thanks, So maybe one other question on the ATRA head and neck cancer data.

You've demonstrated nicely that higher legal frequency correlates with a higher response rates. So my question is now the data has been maturing when additional patients over time have you looked at depth of response and duration of response to see if theres any correlation on those measures where the wheel.

Troy Edward Wilson: Yeah, Joel, thanks for the question, and Mark's here with me. Let me ask him if he can speak to that.

Mark Grasso: Sure. Hey Joel.

Joel Beattie: On partnering, from our standpoint, you know, as we've articulated in the past, doing anything that encumbers rights on TIPI, particularly in the U.S., the hurdle there is high for us, and we see a very attractive go-to-loan strategy, particularly in the initial markets we're talking about here, including relapsed refractory head and neck and AITL. And I would be cautious to set any timing or expectations around anything we might do on the strategic partnering front, whether it be on TIPI Farnham or any of the pipeline assets. I got it. Thanks.

Okay.

Sure Joe Let me, let me, let Antonio answer that one.

Yeah, that's actually very next question. So we we had we're noticing some minor differences. So recall that we may send me in each of these tension last year between this city pipe. Since then and then the 20 put us in.

He we able to.

One thing that patient when they study based on critical mice that goes on we are using they are they all being up 3.5, and thus we will get the good thing for my sense is so if you look at the data from this year.

Joel Beattie: One other question on the HRAF head and neck cancer data. You've demonstrated nicely that higher allele frequency correlates with a higher response rate. My question is, now that the data has been maturing with additional patients over time, have you looked at depth of response and duration of response just to see if there's any correlation on those measures with allele frequency.

You can you you can see that are out of eight patients that they wouldn't that 20 to 35 fold responded that suits seeks respond there seem to attain the how high is on 35 again is multi for instance, you probably will need more patients, but buddy but you still continue that three.

Troy Edward Wilson: Sure, Joel. Let me let Antonio answer that one.

Antonio Gualberto: Yeah, that's actually a very nice question. So, we are noticing some minor differences. So, recall that we made some initial distinction last year between the 35% and then the 20% if we were able to, you know, maintain the patient-on-a-study based on performance status, and we are using the algorithm of 3.5, and that's a good performance status. So, if you look at the data from this year, you can see that out of eight patients that were in that 20 to 35, four responded versus, Again, the small difference is that you probably will need more.

In the high frequency you can see.

But the responsibility on response, you know, obviously, we will need a little bit more time to to see any differences between the two huh.

Last time that a chip personally and into differences in a pretty good if somebody's three so why we couldn't dose to subsets.

But you know.

In any case you know they are good responses seen the 20 to 35 I'm. Good responses on TV thing, how you to them some certified.

Great. Thank you.

Sure. Thanks Joel.

Thank you. Our next question comes from the line of Jay Olson with Oppenheimer. Your line is now open.

Antonio Gualberto: [inaudible]

Joel Beattie: Great, thank you. Thanks, Joel.

Jay Olson: Thank you. Our next question comes from the line of Jay Olson with Oppenheimer. Your line is now open. Oh, hi, thanks for taking the question and congratulations on the data, the triple meeting last week. According to our interviews, it seems like physicians were favorably impressed by the data you presented last week. I was wondering if you could please share with us some of the feedback you received from oncologists attending that meeting and whether or not you think that data might potentially accelerate the enrollment rate in your AIM-HN study.

Hi, Thanks for taking the question and congratulations on the data to Triple meeting last week.

According to our interviews it seems like physicians were favorably impressed by the data you presented last week I was wondering if you could please share with us some of the.

Feedback you received from oncologist attending that meeting and whether or not you think that data might.

Potentially accelerate the enrollment rate in your aim h. and study.

Thanks, Jay for the question and let me, let Antonio speak to your question.

Jay Olson: Thanks Jay for the question, and let me let Antonio speak to your question.

Yes, since I have to say that we have received a very positive feedback you know I'm not just for the deficient.

Antonio Gualberto: Yes, I have to say that we have received very positive feedback, you know, not just for the physicians attending the meeting, but, you know, also the members of our, you know, trial sitting committee, and, you know, so we, as you can imagine, many of the authors were also European authors, so there's actually much assessment for the confirmation of the strategy, the activity of the 600 milligram dose, and the application of the variant allele frequency, so we agree with you that we expect this will, you know, potentially, will, you know, will increase, or we believe will increase the testing or further testing of patients with head and neck, you know, through neck generation sequencing, and that increase in the testing will translate to higher enrollment of eligible patients.

Attending the meeting but also the members. So far why you know trial is sitting committee or do you know so we as you can imagine.

Many of the elsewhere Ulta utopian muscles. So so the such really much excitement for the country to make sure. They start the the activity of the 600 million candles.

On the application while the body frequencies so.

We agree with you that we expect these will you know booked well then Chile you know will in you know it will increase what we believe will increase the tasting or food. The tasting all patients we've hit that mix through next generation sequencing and that increasing that.

Listing will translate.

Two how your.

Jay Olson: Okay, great. Thank you. And then maybe if I could just ask one follow-up question. As you contemplate moving tippi farnab into combination studies for head and neck squamous cell carcinoma, what is the... a TRAS mutant allele frequency cutoff that you would use in those combination studies? Would it be the same that you're using in monotherapy, or would it be different? I'll address that also. So it's actually a very good question, and they are both...

Drum and often that you've been patients.

Okay, great. Thank you and then maybe if I could just asked one follow up as you contemplate moving tipifarnib into combination studies for head and neck squamous cell carcinoma.

What is the.

A traps Newton illegal frequency cut off that you would use in those combination studies would it be the same you are using in monotherapy or would it be different.

The other disciplines and so it's such a big very good question I mean, they're both it kinda like Clinique I got you know, but also there were also can be got rationale. So so currently since they how you'd have been 20, principally frequency is C E C optimal.

Antonio Gualberto: It's kind of like clinical rationale, but also technical rationale. So currently, since the higher than 20% allele frequency is the optimal population for activity as a single agent, we also will continue pursuing monotherapy in that 5% of the population using current technologies, you know, both of the NGS testing in tissue, but also we have available plasmas that we can develop. We can identify, you know, perhaps another 20% of the patients, but as you can imagine, that limit is a technological limit, you know, so you can potentially expand that population going lower than 1%, you know, perhaps, you know, 0.5%. So there's a possibility of expanding the population based on the lower limit of detection of these assays, and we have a number of partners that are perfectly capable of identifying that population. Currently, we are giving that number of, you know, perhaps 20% of het and net because we feel fairly confident with the assays that we have in hand, but, you know, the NGS technology improves every year, and, you know, there could be, you know, potentially, if anything, an increase in the potential target population.

Let's assume offshore activity you have to single agent will we see that we'll continue to swing.

Typically anymore monotherapy in that that's fine, but saying Oh, they population using catering technology as you know the balsam the ngs testing in picchu, but but also we have the available plus my say stuff that we can develop we can identify perhaps.

20% of the patient, but as you can imagine the that that limits. These say 10 net net neurological lead you know sort. So you can you can potentially as panda propylene from going lower down 1%.

Cedar, 0.5%. So so they they say possibility or is pension okay population base on the low low will lead to additional BCC. Some you know we have a number of partners puts it fully capable fleet and define that population. Currently we we are getting the that number perhaps.

20% off hit on it because we feel sadly palm feeling what they say that we have in hand.

But you know that the Ngs technology to anybody yet you know that there could be potentially if anything then on on an increase of the potential target population.

Jay Olson: Okay, great. Thank you for taking the questions and congrats again on the progress. Thank you.

Okay, great. Thank you for taking the questions and.

Grants again on the progress.

Operator: Have a great day!

Thank you thanks Jay.

Joseph Pamp-Dinan: Thank you. As a reminder to ask a question, you will need to press star then 1 on your telephone. Our next question comes from the line of Joseph Pamp-Dinan, with H.C. Wainwright. Your line is now open. Hi guys, this is Pasquale Sansona from the line of Joe.

Thank you as a reminder to ask the question you any to press Star then one on your telephone.

Our next question comes from the line of Joseph Pam.

Yes.

With H.C. Wainwright your line is now open.

Hi, guys. This is this question someone from the line of Joe Congrats.

Joseph Pamp-Dinan: Congratulations on the update on Rane Chang's trial. I have just one question about Rane Chang. So basically, by analyzing tpFARNIM PFS curves based on prior therapies, it looks like that tpFARNIM shows a greater PFS in CKAI failures, so after checkpoint inhibitors. So could this data suggest a potential rationale for combining CKAI with tpFARNIM in order to increase durability of response? Can you please comment on this?

Update on running chain trial I have just a question long run a chance, so basically but analyzing tipifarnib PFS.

Based on prior therapies it looks like the keep Befuddling shows a greater PFS you see a K failures. So after a checkpoint need.

Cookie status suggest the potential rationale of combining a sicad I took tipifarnib him in order to increase durability of response can you. Please comment on this.

Antonio Gualberto: Sure, thanks for the question. I'll let Antonio take that one.

Sure. Thanks for the question, let me, let me, let Antonio take that one.

So I mean, just just to to be clear. We currently you know these she's made required more pages, but we currently do not see deep differences based from the.

Antonio Gualberto: Yeah, so, I mean, just to be clear, we currently, you know, this may require more patients, but we currently do not see the differences based on the prior use of immune therapy versus prior use of 2C-MAP. I think the good news is that with the progression of immunotherapy to the first line, if anything, it further validates the use of tp5-MIP in second line, you know, as monotherapy. That said, you know, I agree with your point that the presence of even a low allele frequency SRAS mutation in the front line will most likely translate to the appearance of progression on the use of immunotherapy, along with, in combination with chemotherapy in the front line. So, there could be an opportunity for potential regimens of chemotherapy, immune therapy, plus tp5-MIP.

Prior to use so immune therapy versus prior year use also to team up I think they good deals since that we did progression won't be immuno therapy to the to the first line.

If anything you don't feel good quality date, they use so tipifarnib opinion in second line you know.

As monotherapy.

That said you know I agree with your point.

The pricing all fall.

Even loyally frequency affects mutation in the phone line that most likely will translate.

To the appearance of progression on the U.S hope immune therapy alone, we committed to a week chemotherapy differently. So so they could be an opportunity or potential regimen. So chemo sit up be immune sit up be blessed to be funny.

Antonio Gualberto: And as I mentioned initially, maybe a high-risk subset could be those patients that, you know, could, for example, be tested in plasma for the presence of circulating SRAS. So, that could be a population that we are estimating to be about 20% of the patients. But as I said previously, that subset can potentially increase, you know, depending on the technological advantages of the use of NGS.

And that we mentioned we need Shelly, maybe a high lease ups. It will be those speeches that Doug do you know who or what does it won't be tested in plasma full depressing books, including interest so so that that could be.

Hopefully choose that we estimated we'll talk about 20% all the patients.

But I wouldn't say three previously or you know that subset.

Potentially increase you know the depending on the technology color balances advantages of the useful for years.

Joseph Pamp-Dinan: All right. Thank you so much.

Joseph Pamp-Dinan: And also a follow-up question. You said that you are studying different combination treatments in preclinical models. So are you seeing more activity when you combine tpFinding with immunotherapeutics?

Alright. Thank you so much ilsa full of course, you said that youre targeting different combination treatments in preclinical models. So I you seem like more TV t. When you combine could be funny, we didn't use a therapeutics or not.

Antonio Gualberto: Thank you for your time.

Joseph Pamp-Dinan: All right, thank you so much, and congratulations on the progress. Thank you. Thank you. Thank you. This concludes today's question and answer session. I would now like to turn the call over to Troy Wilson for closing remarks.

I mean, you kind of trying to anticipate that you know we're going in that Dinesh about four week. We currently have not release and you know that data, but perhaps you can imagine yes. We are doing goals has pretty much something kind of in time.

Alright, thank you so much and congrats on the progress.

Troy Edward Wilson: Thank you, Sarah. Thank you all for the questions and for participating in our call today. Before I conclude, let me just quickly lay out our anticipated milestones over the next 12 months. For Tippi Farnab, additional phase two data in AITL at the ASH meeting in December, regulatory feedback from our phase two trial in AITL in the first half of 2020, additional phase two data in chronic myelomonocytic leukemia or CMML in the first half of 2020, additional phase two data in urothelial carcinoma in For KO-947, our ERK inhibitor, completion of the dose escalation portion of the Phase 1 trial by the end of 2019 or early 2020 and initiation of one or more tumor-specific extension cohorts in 2020.

Thank you. Thank you.

Thank you. This concludes today's question and answer session I would now like to turn the call or what the Troy Wilson for closing remarks.

Thank you Sarah.

Thank you all for the questions and for participating on our call today.

Before we conclude let me just quickly lay out our anticipated milestones over the next 12 months.

For Tipifarnib additional phase two data in AI to yell at the Ash meeting in December .

Regulatory feedback from our phase two trial, then they I T. L. In the first half of 2020 additional phase two data in chronic myeloma citic leukemia or CML in the first half of 2020 additional phase two data and Urothelial carcinoma in 2020 initiation of a proof of concept study in pancreatic cancer in 2020 now.

Potential for full enrollment of they may Chen by the end of 2020.

For care 947, our erk inhibitor completion of the dose escalation portion of the phase one trial by the end of 2019 or early 2020.

And initiation of one or more tumor specific extension cohorts in 2020.

Troy Edward Wilson: And for KO-539, achievement of a recommended Phase 2 dose in 2020. We're planning to be at the Stiefel Healthcare Conference in New York in two weeks, and we look forward to seeing many of you there. In the meantime, if you have any additional questions, please feel free to contact Pete, Mark, or myself. Thank you again, and have a good evening, everyone.

And for Kale 539 achievement of a recommended phase two dose in 2020.

We're planning to be at the Stifel Healthcare Conference in New York in two weeks and we look forward to seeing many of you. There in the meantime, if you have any additional questions. Please feel free to contact Pete Mark or myself. Thank you again and have a good evening everyone.

Ladies and gentlemen, this concludes todays conference call. Thank you for participating you may now disconnect.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

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