Q4 2019 Earnings Call

18, Jira oncology earnings call at this time, all participants are in listen only mode. After the speaker presentation. There will be a question and answer session to ask a question. During this session. Please press star one on your telephone please be advised to today's conference just being recorded if you require any further assistance. Please press star zero I would now like Dan.

Operator: At this time, all participants 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, please press star 1 on your telephone.

Operator: Please be advised that today's conference is being recorded. If you require any further assistance,

Operator: I would now like to hand the conference over to your speaker, Pete Despain, Vice President of Investor Relations. Thank you, Sydney.

Conference over to your Speaker, Pete to Spain, Curis, Vice President of Investor Relations. Please go ahead.

Thank you Sydney, good afternoon, and welcome to occur oncologist fourth quarter full year 2019 conference call joining me on the call concurrent or Dr. Troy Wilson, our President and Chief Executive Officer, Dr., Mark Grasso, Our Chief Financial Officer, and Chief Business Officer, and Dr., Bridget Martell arch acting Chief Medical Officer.

Pete Despain: Good afternoon, and welcome to Kura Oncology's fourth quarter and full year 2019 conference call. Joining me on the call from Kura are Dr. Troy Wilson, our President and Chief Executive Officer, Dr. Mark Grasso, our Chief Financial Officer and Chief Business Officer, and Dr. Bridget Martell, our Acting Chief Medical Officer. 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 expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. 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. With that, I'll now turn the call over to Dr. Troy Wilson, President and CEO of Kura Oncology

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 expectations such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Chris filings with the FCC, which are available from the us.

He see or on the current 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 Carone College.

Troy Edward Wilson: Thank you, Pete, and thank you all for joining us this afternoon. Our mission at Cura is to realize the promise of precision medicines to help patients with cancer lead better, longer lives. Over the past five years, we've made significant strides toward achieving that mission. We have advanced three wholly-owned drug candidates into clinical trials. We've achieved clinical proof of concept in four separate indications with our lead candidate, Tipi Farnab. We have initiated our first registration-directed trial of Tipi Farnab, and we're now actively preparing for a second. And we continue to make progress with our two emerging pipeline programs, our ERK inhibitor, KO947, and our Menin inhibitor, KO539. We've also taken a number of steps to better position the company for our next phase of growth.

Thank you Pete and thank you all for joining US. This afternoon. Our mission Accra is to realize the promise of precision medicines to help patients with cancer lead better longer lives over the past five years, we've made significant strides toward achieving that mission. We've advanced three wholly owned drug candidates into the clinic, we've achieved clinical proof of concept in.

Separate indications with our lead candidate Tipifarnib, we've initiated our first registration directed trial of Tipifarnib and we're now actively preparing for a second and we continue to make progress with our two emerging pipeline programs are erk inhibitor kill 947, and our men in inhibitor Kale five threenine.

Recently, we've also taken a number of steps to better position the company for our next phase of growth.

Troy Edward Wilson: This includes an increasing investment in pre-commercial activities, expansion of our team of medical science liaisons, and importantly, the appointment of our Chief Commercial Officer, Kirsten Flowers. Kirsten joined us last month from Array Biopharma, where she built and led the commercial organization that delivered the impressive launch of Brektovy plus Mektovy for patients with BRAF mutant melanoma in the United States. Previously, she held several commercial leadership roles at Pfizer, including U.S. commercial lead for the launches of Ibran's in breast cancer and LIDA in renal cell carcinoma. Although Kirsten's been on board only for a short time, she's already proven to be a valuable addition to our executive leadership team as we refine our market insights and begin to build the capabilities and expertise required for commercial success and long-term growth. Last month, we also announced that Antonio Gilberto had stepped down as Chief Medical Officer.

This includes an increasing investment in pre commercial activities expansion of our team of medical science Liaisons and importantly, the appointment of our Chief commercial officer Kierston flowers.

Kierston joined US last month from array Biopharma, where she built and led the commercial organization that delivered the impressive launch of Brac Tovey plus mek Toby for patients with B RAF mutant melanoma in the United States previously she held several commercial leadership roles at Pfizer, including U.S. commercial lead for the launches of Ibrance in breast cancer.

And in light a in renal cell carcinoma.

Although kierston spin on board only for a short time. She is already proven to be a valuable addition to our executive leadership team as we refine our market insights and begin to build the capabilities and expertise required for commercial success and long term growth.

Last month, we also announced that Antonio Gilberto had stepped down as chief Medical officer, we want to thank him for his contributions and wish him success in his future endeavors.

Troy Edward Wilson: We want to thank him for his contributions and wish him success in his future endeavors. With this transition, there is an opportunity to sharpen our focus on operational execution across our pipeline. To that end, we're very fortunate to have Bridget Martel, who previously served as our Vice President of Clinical Development and has now stepped up to lead our clinical development organization. Bridget is a proven leader with broad experience in drug development and a track record of success. She has deep familiarity with our organization and pipeline, having served as the clinical lead for our Mennon MLL program over the past two years. Her impact has already been felt on the leadership team, and I'm excited to be working with her more closely. I'm also personally gratified to see how our leadership team and company have pulled together during this transition, and I firmly believe we are stronger and more aligned as a result.

With this transition comes an opportunity to sharpen our focus on operational execution across our pipeline.

To that end, we're very fortunate to have Bridget martell. He previously served as our vice President of clinical development and is now stepped up to lead our clinical development organization.

Bridge It has a proven leader with broad experience in drug development tenant track record of success. She has deep familiarity with our organization and pipeline having served as the clinical lead for a minute MLL program over the past two years.

Impact has already been felt on the leadership team and I'm excited to be working together more closely I am also personally gratified to see how our leadership team and company have pulled together during this transition and I firmly believe we are stronger and more aligned as a result.

Troy Edward Wilson: Now, let me bring you up to speed on each of our programs, beginning with tibiafarnib and H. res mutant solid tumors. However, execution of our registration-directed trial of tipufarnib and HRS mutant head-and-neck squamous cell carcinoma remains our highest priority. The global multicenter trial, AIM-HN, is designed to enroll at least 59 evaluable HNSCC patients with high HRS mutant variant allele frequency who have received prior platinum-based therapy. We anticipate AMHN will complete enrollment in the first quarter of 2021.

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

Execution of our registration directed trial of Tipifarnib, Vinay trusts mutant head and neck squamous cell carcinoma remains our highest priority. The global Multicenter trial, a may Chen is designed to enroll at least 59 invaluable h. an FCC patients with high interest mutant very into little frequency who've received prior platinum based therapy, we end.

To speed Ha, Amy Chen will complete enrollment in the first quarter of Twentytwenty one.

Troy Edward Wilson: As a reminder, we presented data from our Phase II trial of Tipi Farnab in HNSCC patients with high HRAS mutant variant allele frequency at the TRIPLE meeting in October. The interim results of the Phase II RUN-HN trial showed an objective response rate of approximately 50 percent with a median progression-free survival of approximately six months. In comparison, the overall response rates for the three therapies approved for treatment of HN-SCC in the second line, Pembrolizumab, Nivolumab, and Cetuximab, range from 13-16%, with progression-free survival of approximately two months. In December, the FDA granted FASTRAC designation to Tipi Farnab for the treatment of patients with H. res mutan HNSCC after progression on platinum therapy FASTRAC designation highlights the potential for Tipi Farnab to address the unmet need for patients with this devastating disease. The designation offers the opportunity for frequent interactions with the FDA to discuss the drug's development plan to support drug approval, as well as eligibility for rolling submission of a new drug application. Our primary goal for the program is to generate a data package sufficient to support a first application for marketing approval in a transmutant HNSCC.

As a reminder, we presented data from our phase two trial of Tipifarnib in HCC patients with high a trust mutant very into low frequency at the Triple meeting in October the interim results of the phase two run nature and trial showed an objective response rate of approximately 50% with a median progression free survival of approximately six months.

In comparison, the overall response rate for the three therapies approved for treatment of H. and FCC in the second line Pembrolizumab Nivolumab in stocks map ranged from 13% to 16% with progression free survival of approximately two months.

In December the FDA granted fast track designation to Tipifarnib for the treatment of patients with a trust meeting each in FCC after progression on platinum therapy fast track designation highlights the potential for Tipifarnib to address the unmet need for patients with this devastating disease. The designation offers the opportunity for frequent.

Our actions with the FDA to discuss the drugs development plan to support drug approval as well as eligibility for rolling submission of a new drug application.

Our primary goal for the program is to generate a data package sufficient to support a first application from marketing approval in a TRASM even h. NFCC.

Troy Edward Wilson: We also continue to explore options to broaden the market opportunity to other HRS mutant solid tumor indications. In September last year, we reported that an investigator-sponsored trial of tipifarinib in H. rast mutant urothelial carcinomas met its primary efficacy, and, In addition, a number of patients with atras mutant salivary gland cancer were treated with Tipifarnab during the conduct of our Phase II trial, several Further analyses of both studies are ongoing, and we anticipate data will be presented at an upcoming medical meeting. In addition to the opportunity in HRES mutant cancers, the discovery of CXCL12 pathway biomarkers offers the potential to expand the opportunity for tipifarinib to additional hematologic malignancies and solid tumors. For more on our program and advanced T-cell lymphomas, I'll turn the call over to Dr. Bridget Martell. Thank you.

We also continue to explore options to broaden the market opportunity to other HRS mutant solid tumor indications.

In September last year, we reported that an investigator sponsored trial of Tipifarnib in HRS mutant Urothelial Carcinomas met its primary efficacy endpoint. In addition, a number of patients where they trust mutant celebrate Glenn cancer were treated with Tipifarnib during the conduct of our phase two trial, several of whom experience tumor shrinkage and.

Belong disease stabilization.

Further analysis of both studies are ongoing and we anticipate data will be presented at an upcoming medical meeting.

In addition to the opportunity and each breast meat and cancers. The discovery of see Axiall 12 pathway Biomarkers offers the potential to expand the opportunity for Tipifarnib, two additional hematologic malignancies and solid tumors for more on our program and advanced T cell lymphomas, I'll turn the call over to Dr. Bridget Martell.

Dr. Bridget Martell: Thank you, Troy. In December, we reported updated clinical data at the American Society of Hematology Annual Meeting in Orlando, showing robust and durable activity from tippy-farnab as monotherapy for relapsed or refractory angio-immunoblastic T-cell lymphoma, or AITL. Our data presented by Dr. Thomas Witzig, a hematologist at the Mayo Clinic and a principal investigator in the trial, demonstrated an objective response rate of approximately 50% in a heavily pretreated patient population with a median of three prior regimens. Additionally, enhanced anti-tumor activity was observed in the 10 clinical trial patients who carried mutations in the killer cell immunoglobulin-like receptor, or KIR, a CXCL pathway These patients had an overall response rate of 70% and a complete response rate of 40%. We believe our data, coupled with the high unmet medical need for these patients, support our efforts to expand the development of tippi farnib beyond our initial focus on H. rast mutant solid tumors. As a reminder, peripheral T cell lymphomas comprise up to 20% of all aggressive non-Hodgkin lymphomas and consist of many different subtypes of fast-growing lymphomas. Outcomes for these patients are poor; five-year survival is approximately 30%. Although several drugs have been approved in the relapsed and or refractory setting, none have led to survival benefits.

Thank you Troy in December we reported updated clinical data at the American Society of Hematology annual meeting in Orlando.

Showing robust and durable activity from Tipifarnib as a monotherapy in relapsed or refractory angio amenable plastic T cell lymphoma, our ATM.

Our data presented by Dr. Thomas was sick Hematologist at the Mayo clinic, and a principal investigator and the trial demonstrated an objective response rate of approximately 50% and a heavily pre treated patient population with the median it was three prior regimens.

Additionally, enhanced anti tumor activity was observed in the 10 clinical trial patients who carried mutations in the killer cell immunoglobulin like receptor or care acxioms pathway associated biomarker.

These patients had an overall response rate of 70% and a complete response rate of 40%.

I believe our data coupled with the high unmet medical need for these patients support our efforts to expand the development of Tipifarnib beyond our initial focus and each BRAF mutant solid tumors.

As a reminder, peripheral T cell lymphoma comprise up to 20% of all aggressive non hodgkin lymphoma and consist of many different subtype a fast growing lymphoma.

Outcomes for these patients are poor five year survivals approximately 30%.

Although several drugs have been approved in the relapsed and or refractory setting non has led to survival benefit.

Dr. Bridget Martell: In addition, the National Comprehensive Cancer Network guidelines currently recommend clinical trials for these patients. On another note, before we continue, significant advances in the genetic landscape of T cell lymphomas have led to a revision of the World Health Organization classification and the introduction of new terminology. As such, we have modernized our terminology going forward in an effort to align with the latest WHO classification.

In addition, the national comprehensive cancer network guidelines currently recommend clinical trials for these patients.

On another note before we continue significant advances in the genetic landscape of T cell lymphoma have led to a revision of the World Health organization classification, and the introduction of new terminology.

As such we have modernized our terminology going forward in an effort to align with the latest W.H.O. classification.

Dr. Bridget Martell: For instance, instead of AITL and AITL-like lymphomas, you'll hear us refer to a more comprehensive classification of advanced nodal lymphomas of the T follicular helper, or TFH, phenotype, which includes AITL. Following positive feedback from our end of Phase II meeting with the FDA, we are now preparing to initiate a registration-directed trial of titifarnib in advanced nodal lymph This single-arm trial will target enrollment of approximately 128 patients who are relapsed or refractory to at least one prior systemic cytotoxic therapy. Here we will investigate two independent primary objectives, objective response rate in all patients enrolled and objective response rate in patients who carry a cure mutation. Patients will be enrolled on the basis of a pathologic diagnosis of the disease.

For instance, instead of AI, TL and AI to yell like lymphoma.

Hijras referred to a more comprehensive classification of advance nodal lymphoma is a key follicular helper Rts age phenotype, which includes 80 out.

Following positive feedback from our end of phase two meeting with the FDA. We are now preparing to initiate a registration directed trial of Tipifarnib and advanced nodal lymphomas T F H origin, including I.T. out.

The single arm trial will target enrollment of approximately 120 patients or relapsed or refractory to at least one prior systemic cytotoxic therapy.

Here, we will investigate two independent primary objective objective response rate and all patients enrolled and objective response rate in patients who carry experimentation.

Patients will be enrolled on the basis of a pathlogic diagnosis of disease.

Dr. Bridget Martell: Your mutational status will be determined retrospectively. Each of the two primary objectives has a null hypothesis of 9%, and each can be met independently. We believe the feedback from our end of Phase II meeting with the FDA indicates that the trial, as designed, could support an NDA-seeking accelerated approval for tipifarnab monotherapy in lymphomas of PFH origin and or those with cure mutations. We are currently conducting startup activities and expect to initiate the registration-directed trial in the second half of the year. With that, I'll turn the call back over to Troy.

Here mutational status will be term BB determined retrospectively.

Each of the two primary objectives has a no hypothesis of 9% and each can be met independently.

We believe the feedback from our end of phase two meeting with the FDA indicates that the trial as designed could support and antigay seeking accelerated approval for Tipifarnib monotherapy in lymphomas, Fps, H origin, and or lymphomas, STS H origin Mccarran mutation.

We are currently conducting startup activities and expect to initiate the registration directed trial and the second half of the year.

With that I'll turn the call back over to Troy.

Troy Edward Wilson: Thank you, Bridget. We believe that CXCL12 pathway biomarkers may have the potential to unlock the therapeutic value of farnesyltransferase inhibitors across a range of hematologic and solid tumor indications. One of the indications of particularly high interest is pancreatic cancer. The currently reported five-year survival rate for pancreatic cancer remains at a dismal 10%, and there is an urgent need to identify new molecular mechanisms to drive anti-tumor activity and improve survival.

Thank you Bridget we believe this that 612 pathway Biomarkers may have the potential to unlock the therapeutic value a furnace will transfer ace inhibitors across a range of metal logic consolidation we're indication.

One of the indications are particularly high interest is pancreatic cancer. The currently reported five year survival rate for pancreatic cancer remains at a dismal, 10% and there's an urgent need to identify new molecular mechanisms to drive anti tumor activity and improve survival.

Troy Edward Wilson: Recall a year ago we reported a retrospective analysis of prior clinical data that appears to identify a potential association between CXCL12 expression and clinical benefit from tipifarnib in patients with pancreatic cancer. Since then, we've continued to conduct additional preclinical work to validate tipifarnib in a CXCL12-high subpopulation of pancreatic cancer patients. Recently, we generated preclinical data showing that tipifarnab can block the production of CXCL12 by activated pancreatic stellate cells.

Recall, a year ago, we reported a retrospective analysis of prior clinical data that appears to identify a potential association between CXC IL 12 expression and clinical benefit from Tipifarnib in patients with pancreatic cancer.

Since then we've continued to conduct additional preclinical work to validate tipifarnib in a CXC all 12 high subpopulation of pancreatic cancer patients recently, we generated preclinical data showing that tipifarnib can block production of see Axiall 12 by activated pancreatic still itself. In addition, we've observed the potential.

Troy Edward Wilson: In addition, we've observed the potential for synergy between tipifarnab and chemotherapy in preclinical models of pancreatic cancer. These data bolster our retrospective analysis of the prior clinical data and further support our decision to conduct a proof-of-concept trial of Tipi Farnab in combination with chemotherapy in the second-line setting for the treatment of advanced pancreatic cancer. Preparations are underway to initiate this trial in the second half of 2020. We are very encouraged by the high level of clinical activity observed thus far in both solid tumors and heme malignant. With four positive Phase II studies now achieved, we believe Farnesil transferase inhibition has the potential to deliver multiple expansion opportunities in long-term growth. Now, let's turn our attention to our emerging pipeline programs, beginning with our ERK inhibitor, KO947.

For synergy between Tipifarnib in chemotherapy in preclinical models of pancreatic cancer.

These data bolster our retrospective analysis for the prior clinical data and further support our decision to conduct a proof of concept trial of Tipifarnib in combination with chemotherapy in the second line setting for the treatment of advanced pancreatic cancer preparations are underway to initiate this trial in the second half of Twentytwenty.

We're very encouraged by the high level of clinical activity observed thus far in both solid tumors in heme malignancies with for positive phase. Two studies now achieved we believe pharmacell transferase inhibition has the potential to deliver multiple expansion opportunities and long term growth.

Now, let's turn our attention to our emerging pipeline programs, beginning with our erk inhibitor care 947.

Troy Edward Wilson: K0947 is a potent and selective small molecule inhibitor of ERK, a protein kinase that represents a central node on the mitogen-activated protein kinase or MAPK pathway, a well-established pathway in human cancer. We have been evaluating KO-947 in a Phase I dose escalation study and believe we have identified a recommended Phase II dose for KO-947 as mono Recently, however, we observed a dose-limiting serious adverse drug reaction in a single patient enrolled in the study. Although patients were permitted to remain on therapy, we voluntarily paused enrollment.

Kevin I four seven as a potent and selective small molecule inhibitor ERC a protein kinase that represents a central node on the might engine activated protein kinase or map K pathway, a well established pathway in human cancers.

We have been evaluating kao 947 in a phase one dose escalation study and believe we have identified a recommended phase two dose for care 947 as a monotherapy.

Recently, however, we observed a dose limiting serious adverse drug reactions in a single patient enrolled on the study although patients were permitted to remain on therapy, we voluntarily paused enrollment. We also met with FDA to discuss the safety observation and consistent with our actions. The trial was placed on a partial clinical hold however, based.

Troy Edward Wilson: We also met with FDA to discuss the safety observation, and consistent with our actions, the trial was placed on a partial clinical hold. However, based on our assessment of the available pharmacovigilance data, we believe we have a path forward to resume the trial with additional safety monitoring in place. We're working to lift the hold and resume the study at the recommended phase 2 dose of KO-947 as a monotherapy. Upon FDA agreement, we plan to initiate an expansion cohort to evaluate KO-947 in HNSCC and esophageal squamous cell carcinoma patients with 11q13 amplifications, genetically defined populations identified as particularly sensitive to KO-947 monotherapy in preclinical models. Our other emerging drug candidate is KL539, a first-in-class, potent, and selective small-molecule inhibitor of the Menin-MLL protein-protein interaction.

On our assessment of the available Pharmacovigilance data, we believe we have a path forward to resume the trial with additional safety monitoring and place we're working to lift the hold and resume the study at the recommended phase two dose of care 947 as a monotherapy.

Upon FDA agreement, we plan to initiate an expansion cohort to evaluate care 947 in h. in FCC and a softer deal squamous cell carcinoma patients with 11 to 13 amplifications genetically defined populations identified as particularly sensitive to Q 947 monotherapy.

In preclinical models.

Our other emerging drug candidate is scale 539, a first in class potent and selective small molecule inhibitor of the men in MLL protein protein interaction preclinical data support the potential for potent anti tumor activity in genetically defined subsets, such as MLL fusions and rearrangements as well as end.

Troy Edward Wilson: Preclinical data support the potential for potent anti-tumor activity in genetically defined subsets, such as MLL fusions and rearrangements, as well as NPM1 mutations. Despite a number of advancements in the treatment of patients, with AML, the 5-year survival rate for people 20 years and older with AML is less than 25%. KO539 has received orphan drug designation from the FDA for the treatment of acute myeloid leukemia, recognizing its potential to address a population of patients with high unmet needs. We dosed the first patient in our Phase I-II clinical trial of KO539 in relapsed and refractory AML in September 2019, and the trial continues in dose escalation. Our goal is to reach a recommended Phase II dose or a maximum tolerated dose with the potential to enrich NPM1 mutant AML and MLL-rearranged genetically-defined subgroups later this year. We continue to believe that K0539 represents a differentiated approach to the treatment of patients with AML. We remain enthusiastic about its potential and look forward to sharing updates with you in the months ahead. With that, I'll now turn the call over to Mark Grasso for a discussion of our financial results for the fourth quarter and full year 2019.

PMN one mutations.

Despite a number of advancements in the treatment of patients with AML. The five year survival rate for people 20 years and older with AML is less than 25%.

539 has received orphan drug designation from the FDA for the treatment of acute myeloid leukemia, recognizing its potential to address a population of patients with high unmet need.

We dose the first patient in our phase one two clinical trial of scale 539 in relapsed and refractory AML in September 2019, and the trial continues in dose escalation. Our goal is to reach a recommended phase two dose or a maximum tolerated dose with the potential to enrich and NPM, one mutant ammo and MLL rearranged.

Genetically defined subgroups later this year.

We continue to believe the Kao 539 represents a differentiated approach for the treatment of patients with a ml. We remain enthusiastic about its potential and look forward to sharing updates with you in the months ahead with that I'll now turn the call over to Mark Grasso for a discussion of our financial results for the fourth quarter and full year 2019.

Mark Grasso: Thank you, Troy, and good afternoon, everyone. I'll provide a brief overview of our financial results here on the call and invite you to review our 10-K file today for a more detailed discussion. Research and development expenses for the fourth quarter of 2019 were $13.5 million, compared to $12.1 million for the fourth quarter of 2018. R&D expenses for the full year 2019 were $47.8 million, compared to $46.8 million for the prior year. The increases in R&D expenses for the year were primarily due to an increase in clinical development activities related to our registration-directed trial of Tiput-Farnab, offset by decreases in preclinical development for KO539, companion diagnostics, and clinical supply manufacturing activities for Tiput-Farnab, and non-cashier-based compensation.

Thank you Troy and good afternoon, everyone.

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

Research and development expenses for the fourth quarter of 2019 for $13.5 million compared to $12.1 million for the fourth quarter of 2018.

R&D expenses for the full year 2019 were $47.8 million.

Imperative $46.8 million for the prior year.

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

Offset by decreases in preclinical development for clarify Threenine companion diagnostics and clinical supply manufacturing activities for Tipifarnib and noncash share based comp compensation.

General and administrative expenses for the fourth quarter of 2019 were $5.5 million compared to $4.6 million for the fourth quarter 2018.

Mark Grasso: General and administrative expenses for the fourth quarter of 2019 were $5.5 million, compared to $4.6 million for the fourth quarter of 2018. G&A expenses for the full year 2019 were $19.7 million, compared to $16.1 million for the prior year. The increase in G&A expenses was primarily due to increases in non-cashier-based compensation and personnel costs.

DNA expenses for the full year 2019 were $19.7 million compared to $16.1 million for the prior year.

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

Net loss for the fourth quarter of 2019 was $17.9 million compared to a net loss of $16.1 million for the fourth quarter 2018.

Loss for the full year 2019 was $63.1 million compared to a net loss of $64.4 million for the prior year.

Mark Grasso: The net loss for the fourth quarter of 2019 was $17.9 million compared to a net loss of $16.1 million for the fourth quarter of 2018. The net loss for the full year 2019 was $63.1 million compared to a net loss of $64.4 million for the prior year. The net loss for the fourth quarter and full year 2019 included a non-cash, share-based compensation expense of $2.4 million and $9.4 million compared to $1.7 million and $8.7 million for the same periods in 2018. Our cash, cash equivalents, and short-term investments were $236.9 million as of December 31st, 2019, compared with $179 million as of December 31st, 2018. Following recent regulatory feedback regarding our proposed registration-directed trial on advanced T-cell lymphomas, we are updating our CASH guidance. We believe our cash, cash equivalents, and short-term investments will be sufficient to fund our operating expenses and capital expenditure requirements into 2022. With that, I will now turn the call back over to Troy.

Net loss for the fourth quarter and full year 2019 included noncash share based compensation expense of $2.4 million and $9.4 million compared to $1.7 million and $8.7 million for the same periods in 2018.

Our cash cash equivalents in short term investments were $236.9 million as of December 30, Onest 2019, compared with $179 million as of December 30, Onest 2018.

Post receipt of regulatory feedback regarding our proposed registration directed trial on advanced T cell lymphomas, we're updating our cash guidance.

We believe our cash cash equivalents in short term investments will be sufficient to fund our operating expenses in capital expenditure requirements into 2022 with that ill now turn the call back over to Troy.

Thanks, Mark before we jump into the queue in a session. Let me lay out our anticipated milestones for the year ahead.

Our tipifarnib additional phase two data in a trust mutant solid tumors, including HRS mutant Urothelial carcinoma in 2020.

Initiation of a registration directed trial and advanced T cell lymphoma in the second half of 2020 initiation of a proof of concept study in pancreatic cancer in the second half of 2020.

Additional phase two data in chronic model monocytic leukemia, and Twentytwenty and the potential for full enrollment today may Chen in the first quarter of Twentytwenty one.

Troy Edward Wilson: Thanks, Mark. Before we jump into the Q&A session, let me lay out our anticipated milestones for the year ahead.

For cable 947 opened an expansion cohort of H. NFCC in a softer deal squamous cell carcinoma patients with 11 to 13, amplifications and 2020 and for Kale 539 at achievement of a recommended phase two dose by the end of Twentytwenty with that operator, we're now ready for questions.

Operator: For Tippi Farnab, additional phase 2 data in H.R.S. mutant solid tumors, including H.R.S. Mutant urethelial carcinoma in 2020. Initiation of a registration-directed trial in advanced T-cell lymphoma in the second half of 2020. Initiation of a proof-of-concept study in pancreatic cancer in the second half of 2020 Additional Phase II data in chronic myelomonocytic leukemia in 2020 And the potential for full enrollment in AMHN in the first quarter of 2021 And for KO-539, achievement of a recommended phase two dose by the end of 2020. So with that operator, we're now ready for questions.

Thank you as a reminder to ask a question you want me to press Star one on your telephone.

Withdraw your question please press the pound.

Our first question comes from Jonathan Chang with SVB Leerink. Your line is open.

Hi, guys. This is David Rouge on for Jonathan Thanks for taking our questions.

I guess first could you provide any additional color on the partial clinical hold.

So you though was observed.

Just kind of.

Any color on what that was then does this.

Does this impact the.

Condition like what are the condition of the hold I guess.

Operator: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, please press the pound. Our first question comes from Jonathan Chang with SVB Learing. Your line is open. Hey guys, this is David Ruchon speaking for Jonathan. Thanks for taking our questions. I guess, first, could you provide any additional color on the partial clinical hold and the SAE that was observed? Just kind of any color on what that was and does this... Does this impact the condition, like what are the conditions of the hold, I guess?

Sure. Thank you for the question this is Bridget.

Thank you.

You know as.

With any clinical trial, we don't really does Scott's clinical trial data outcomes, whether its safety or efficacy, but suffice it to say we're confident that this will be.

It is and collaborative discussion with the FDA and we're confident that will move into our expansion cohort shortly.

Okay could you.

Could you talk a little bit in general on how this impacts the development strategy overall and.

How you might be potentially thinking about combination studies down the road.

So from my monastery for perspective before I get to the combination I think the goal of any phase one trial is studying a new chemical entity as a monotherapy and reaching a recommended phase two dose often times by by virtue of a dose limiting toxicity and so based on that.

Bridget: Thank you for the question. This is Bridget.

Bridget: You know, as with any clinical trial, we don't really discuss clinical trial data outcomes, whether it's safety or efficacy. But suffice it to say, we're confident that this will be an iterative and collaborative discussion with the FDA, and we're confident that we'll move into our expansion cohort shortly.

We know that we have achieved that and we can now look to combination therapies that would be in concert with the mechanism of this drug and both benefit patients and have sufficient safety profile.

Bridget: Okay, could you talk a little bit in general about how this impacts the development strategy overall and how you might be potentially thinking about combination studies down the road?

I think David this is Troy got to add to that I don't think it changes at all our strategy from a development perspective, we've been consistent that we see an opportunity to evaluate care 947 at a recommended phase two dose in these 11 to 13 amplified patients that is.

Troy Edward Wilson: So from a monotherapy perspective, before I get to the combination, I think the goal of any phase one trial is to study a new chemical entity as a monotherapy and reach a recommended phase two dose, oftentimes by virtue of dose-limiting toxicity. And so, based on that, we know that we have achieved that, and we can now look to combination therapies that would be in concert with the mechanism of this drug and both benefit patients and have a sufficient safety profile.

Those patients were suggested by the extensive preclinical modeling that we did.

That we've spoken to over the past several years.

Troy Edward Wilson: I think, David, this is Troy, just to add to that. I don't think it changes at all our strategy from a development perspective. We've been consistent in saying that we see an opportunity to evaluate KO-947 at a recommended phase 2 dose in these 11q13 amplified patients. That is, those patients were suggested by the extensive preclinical modeling that we did, you know, that we've spoken to over the past several years. As Bridget mentioned, we need to work internally and with FDA to lift this clinical hold, and then we look forward to moving forward into those populations. But it doesn't really change the development strategy in any way. It is, you know, the goal is to identify a recommended phase 2 dose, and we've done that. We do need to work through this, though, with FDA.

As Bridget mentioned, we need to work.

Internally and with the FDA to to lift this clinical hold and then we look forward to moving forward into those populations, but it doesn't it doesn't change the development strategy really in any way it is.

The goal is to identify a recommended phase two dose than we've done that we do need to work through this though with FDA.

Got it understood. Thank you.

I guess moving out from that could you.

Could you talk about if the image and study is positive what are the next steps for Tipifarnib and screen itself.

Head and neck, and what are the opportunities for frontline expansion and and kind of other expansion opportunities beyond as you see a gen.

Sure that it's a good question.

And I think we're guided by by three different things were guided by what we've seen clinically.

Both in Rene Chan and in it and in a May Chen we're guided by the evolving landscape of standard of care and then were guided by our preclinical data.

Troy Edward Wilson: Got it, understood, thank you. I guess, moving on from that, could you talk about if the AMHN study is positive, what are the next steps for tibiafarnib and squamous cell, head and neck, and what are the opportunities for frontline expansion and kind of other expansion opportunities beyond SCCHN?

Clearly there I think one has to acknowledge that immune therapy and combinations with chemotherapy are moving to the frontline.

Troy Edward Wilson: Sure, it's a good question, and I think we are guided by three different things. We're guided by what we've seen clinically, both in RUN-HN and in AIM-HN. We're guided by the evolving landscape of standard of care, and then we're guided by our preclinical data. Clearly, I think one has to acknowledge that immune therapy and combinations with chemotherapy are moving to the front line. We've talked in the past about evaluating tipifarnib in combination with various agents, including chemotherapy, targeted therapy, and potentially immune therapy. We're not yet at a point where I think we can articulate to you exactly what the clinical studies would look like, but it is something of interest to us. And as I mentioned in my prepared remarks, you know, what we are also encouraged by is that we see a level of clinical activity as we look across solid tumors, whether it may be head and neck, urethelial, or salivary.

And we've talked in the past about evaluating tipifarnib in combination with various agents, including chemotherapy targeted therapy and potentially immune therapy, we're not yet at a point, where I think we can articulate to you exactly what the clinical studies would look like but it is it is something.

Interest to us and as I mentioned in the prepared remarks.

What we're also encouraged by is that we see a level of clinical activity as we look across solid tumors, whether it may be head and neck Urothelial salivary.

And so we also want to we also want to be mindful of that and.

This this is going to be an evolution.

Troy Edward Wilson: And so we also want to be mindful of that, with the research and development group, as well as Kirsten's group, the commercial group, to plot out the next step. So, I think, you know, we'll have more to say about that, perhaps later in the year. At this point, though, you know, we definitely see an opportunity to move to additional indications and to earlier in the treatment paradigm, you know, if and when AMHN is successful.

With the research and development group.

As well as cure since group the commercial group to plot out the next steps.

So I think we'll have more to say about that perhaps later in the year on at this point, though we definitely see an opportunity to move to additional indications into two earlier in the treatment paradigm.

If and when they may trend is successful.

Got it thanks, Troy I appreciate that and we will look forward to argue later.

Troy Edward Wilson: Got it. Thanks, Troy. We appreciate that. And we will look forward to talking to you later.

Great. Thank you.

Thank you and our next question comes from Chris Shibutani with Cowen. Your line is now open.

Troy Edward Wilson: Great, thank you.

Operator: Thank you. And our next question comes from Chris Shibutani with Cohen. Your line is now open.

Thank you very much two questions on the.

Operator: Thank you very much. Two questions. On the reclassification, the new terminology for the lymphoma genetic landscape T-cell there,

Reclassification, the new food terminology for that lymphoma genetic landscape T cell there should we think that that reclassification, possibly at all changes the potential denominator of patients that you might be thinking would be eligible for your therapies or is that just true true not related and again youre.

Troy Edward Wilson: What do you think is the potential denominator of patients that you might be thinking would be eligible for your therapies, or is that just true-true, not related, and again, your sort of biomarker-guarded strategy still gives you the same range of patients when you think about the ultimate clinical trial or commercial opportunity?

Our sort of Biomark regarded strategy still gives you seem scope of patients. When you think about the ultimate either clinical trial or commercial opportunity.

Troy Edward Wilson: Yeah, Chris, thanks for the question. The literature references suggest that there are, you know, 3,500 to 4,000 patients per year in the U.S. with PTCL, and equivalent numbers, you know, in ex-U.S. territories. Our best estimate of the eligible patient population under the new classification, you know, the nodal T-cell lymphomas of the T-follicular helper phenotype, is approximately 30% of that population. It may be a little higher outside the U.S., but it probably doesn't change what we've been guiding to in terms of the eligible population. It's just, you know, the physicians and the KOLs who treat this disease are very active in, as you know, challenging for new therapies, new biomarkers, new ways of classifying patients.

Yes, Chris Thanks for the question so.

The the literature references suggest that there are.

3500 to 4000 patients per year in the us with PTCL.

Equivalent numbers.

In in ex US territories, our best estimate of the of the eligible patient population under the new classification.

The nodal T cell lymphoma as of the T. Follicular helper phenotype is approximately 30% of that population it maybe a little higher outside the us.

But it probably doesn't change what we've been guiding to in terms of the eligible population. It's just.

The the physicians and the care wells, who treat this disease are very active at as you know at at challenging for new therapies, New Biomarkers, new ways of classifying patients.

Troy Edward Wilson: And so, you know, this, in our way of thinking, this actually probably helps us because, again, the entry criteria into the study are a pathological diagnosis that's consistent with the WHO criteria rather than a retrospective analysis of the biomarker. In that way, it's different than the AMHN study. Does that help answer your question? Yeah, no, it does seem...

And so this in our way of thinking this actually probably helps us because again, it's the the entry criteria onto the study is a pathological diagnosis that's consistent with the Whr criteria, then with a with a retrospective analysis of the biomarker in that way, it's different than the aim HM.

Study does that help answer your question.

Yes, no it does seem to be little bit more of a classification difference just didnt know whether or not it had any implications for how we should be thinking about the opportunity and we'll certainly continue to follow that if I could ask a follow up question.

Troy Edward Wilson: There seemed to be a little bit more of a classification difference, but I just didn't know whether or not it had any implications for how we should be thinking about the opportunity. And we'll certainly continue to do that.

Operator: If I could ask a follow-up question, AIM-HN and enrollment, you have some clear goals for the patient numbers, at a minimum, and the timelines, which I think you've reiterated now to be the first quarter of the year.

Same age and enrollment you have some clear goals for the patient numbers at a minimum and the timelines, which I think you reiterated now to be first quarter of 2021.

Operator: of 2021. You also mentioned that you have some additional fresh eyes on.

You also mentioned that you have some additional fresh eyes on potentially the situation, particularly with bridges and Kirsten with persons pedigree coming from array certainly is something that I think for the commercial viewpoint could be potentially valuable can you tell us about.

Operator: Potentially, the situation, particularly with Bridget and Kirsten, with Kirsten's pedigree coming from Array, is certainly something that needs to be addressed.

Operator: This is something that, from a commercial viewpoint, could be potentially valuable. Can you tell us about any of the new...

Any of the new insights or strategies that you're perhaps putting into place that continue to perhaps give you confidence in being able to make those timelines I think in the past you talked about kind of trying to figure out how patients who are either in the phase two versus the phase three study often there were questions of perhaps sicker patients whether they were eligible or.

Operator: There are a number of strategies that you're perhaps putting into place that continue to perhaps give you confidence in being able to make those timelines. I think in the past you talked about kind of trying to figure out how patients who are either in the Phase II versus the Phase III study often had questions about perhaps sicker patients, whether they were eligible or not.

How are you balancing those factors, particularly with the new voices at the table that you have thanks.

Troy Edward Wilson: Thank you for the two voices at the table that you have.

Yes, thanks for the question so.

Troy Edward Wilson: Yeah, thanks for the question. So, maybe to take the questions in reverse, we are delighted, you know, to have Bridget in this expanded role, partnering with, you know, not only with Kirsten but with Kathy Ford, you know, our Chief Operating Officer. And we are, you know, I said it in the prepared remarks, and I'll reiterate it, it is our highest priority at the company. And, you know, we are focused on a number of aspects of that study, including, you know, the number of patients screened. Given that we are screening in the front line, you know, we have to be mindful of the impact of the evolving treatment landscape in the front line. And it's very much, you know; it's the number one thing we talk about at the company.

Maybe to take the questions and reverse so we are delighted to have bridge. It in this expanded role partnering with not only with kierston, but with Kathy forward, our Chief operating officer, and we are I said it in the prepared remarks and I'll reiterate it it is our highest priority at the.

Company and we are we are focused on a number of aspects of that study including numbers of patients screened.

Given that we're screening in the front line, we have to be mindful of of the impact of kind of the evolving treatment landscape in the frontline.

And it's very much it's the number one thing we talk about at the company.

At this point I'm not sure I can give you a lot more clarity we are where at a point now where nearly every site is open that is going to be open there may be a straggler or too we continue to try to get more out of our sites in terms of screening patients and too.

Troy Edward Wilson: At this point, I'm not sure I can give you a lot more clarity. We are, you know, at a point now where nearly every site is open that is going to be open. There may be a straggler or two. We continue to try to get more out of our sites in terms of screening patients and, you know, doing the best we can to deliver on the timeline that we've articulated. But I can't get much more into the specifics at this point.

I'm doing the best we can to deliver on the on the timeline that we've articulated.

But I can't get much more into the specifics at this point.

Yes, I do think and I said again I said this in the prepared remarks and ill and I'll emphasize it.

Troy Edward Wilson: I do think, and again, I said this in the prepared remarks, and I'll emphasize it, it's been, I think, terrific to have, you know, Bridget come in and have the team really come together and not only look at AMHN but across the entire pipeline with lots of ways of creating value, lots of kinds of interesting inflection points throughout the year. And I've been, you know, as CEO, just really gratified to see the extent to which the team has pulled together to say how we can do better, do different, and better if needed. So I think we'll be in a stronger position, you know, going forward through the rest of this year and into next year. Great, thanks. It's great to see bench strength improve, and we'll keep an eye on that trial enrollment. Thank you, Troy. Thanks, Chris.

It's been I think terrific to have.

Bridget come in and have the team really come together and not only look at CMH yen, but across the entire pipeline.

With lots of ways of creating value lots of kind of interesting inflection points throughout the year and I've been just as as CEO, just really gratified to see the extent to which the team has pulled together.

To say, how can we do better do different in better if needed.

So I think we'll be in a stronger position going forward through the rest of this year and into next year.

Great. Thanks, it's great to see the bench strength improved and we'll keep an eye on that trial enrollment. Thank you Tracy.

Thanks, Chris.

Thank you. Our next question comes from Tyler Van Buren with Piper Sandler Your line is open.

Operator: Thank you. And our next question comes from Tyler Van Buren with Piper Sandler. Your line is open.

Hey, guys. Good afternoon had another one HM, especially with the encouraging updates on enrollment and Precommercial activities.

So can you just confirm that it's still.

Operator: Hey guys, good afternoon. I had another one on AIM-HM, especially with the encouraging updates on enrollment and pre-commercial activities.

15 responses required to reject the middle hypothesis and if the 15th response comes tomorrow.

Troy Edward Wilson: So can you just confirm that it's still 15 responses required to reject the null hypothesis? And if the 15th response comes tomorrow, can you start the rolling NDA submission immediately? Are you guys in a situation where you can do that?

And you start the and the the rolling NDA submission.

Immediately or you guys in.

Situation, where you can do that and how long would that take.

Troy Edward Wilson: And how long would that take in terms of timelines? And specifically, you also mentioned eligibility for NDA rolling submission. How is that determined?

In terms of timelines and specifically you also mentioned eligibility for Mds Rolling submission how is that determined.

Right. Okay. So Tyler thanks for the question you've got a few things kind of packed in there.

Troy Edward Wilson: Right. So, Tyler, thanks for the question. You've got a few things kind of packed in there.

Troy Edward Wilson: So, you're correct. Fifteen confirmed responses are what are needed to reject the null hypothesis. Those have to be centrally adjudicated and reviewed by the Data Safety Monitoring Committee. So, if and when that happens, we are assuming that the DSMB will notify the company, and that the company has to both notify the agency and the investigators in the study. We would, you know, we would then anticipate that we would make that information public. I think it's, let me just say it's premature, I think, to talk about the timing of the submission. We are, we were, you know, gratified to get the Fast Track designation. I think that's a recognition by FDA of the unmet medical need and the clinical activity that was demonstrated in Phase 2. We continue to push to take advantage of any sort of regulatory advantage that would be available, not only in head and neck, but now you'll see in T-cell lymphoma. That's a bit of a work in progress. But, you know, I don't want to; I don't want to look too far into the future.

So.

You're correct 15 confirmed responses are what are needed to reject the NOL hypothesis those have to be centrally adjudicated.

And reviewed by the data safety monitoring committee so.

If and when that happens we are assuming that the DSMB be will notify the company that the company has to both notify the agency and the investigators on the study.

We would we would then anticipate that we would make that information public.

I think its let me just say, it's premature I think to talk about the timing of the submission.

We are we were gratified to get the fast track designation I think thats a recognition by FDA of the unmet medical need and the clinical activity that was demonstrated in phase two we continue to push to take advantage of any sort of regulatory.

Advantage that would be available not only in head and neck, but now you'll see it in T cell lymphoma.

Thats a bit of work in progress, but but I don't want to I don't want to look too far into the future.

Troy Edward Wilson: Yeah.

Troy Edward Wilson: Our focus at the moment is on that execution point that you mentioned, and we'll keep it there. We are trying to set the company up for success if and when AMHN is positive.

Our focus at the moment is on that execution point that you mentioned and.

We'll keep it there we are trying to set the company up up for success, if and when Amgen is positive.

Troy Edward Wilson: Okay, that's helpful. And maybe just a quick second one.

Okay. That's helpful. Maybe just some quick second one on men MLL can you give us any sort of color where you are in terms of.

Bridget: On men and MLL, can you give us any sort of color on where you are in terms of the dose range or what dose cohort you're at? And also, whether you expect any responses or significant clinical benefit in this initial non-enriched patient population?

The dose ranging or what dose cohort.

And also if you expect any responses are significant clinical benefit in this initial non enriched patient population.

Hi, Tyler this is president I can I can address that question for you. So we are in dose escalation in the face some portion of the trial. It isn't all comer AML as we had stated before however, investigators do you know that we are.

Bridget: Hi Tyler, this is Bridget. I can address that question for you. So we are in dose escalation in the phase one portion of the trial. It is an all-comer AML, as we have stated before. However, investigators do know that we are targeting a certain population, so they will choose their patients as appropriate for the dose escalation trial. We don't currently disclose where we are in that dose escalation trial. We can just say that it is progressing as planned.

Targeting a certain population so they will choose their patient as appropriate onto the dose escalation trial. We don't disclose currently where we are in that dose escalation. We can just say that is progressing as planned.

Great. Thanks, so much guys.

Troy Edward Wilson: Great. Thanks so much, guys. Thanks, Tyler. Thank you. And our next question comes from Jay Olsen with Oppenheimer. Your line is now open. Oh, guys, congratulations on all the progress and new additions to your leadership team. I wanted to follow up on the positive feedback from the FDA at your end-of-phase 2 meeting and comments they made about the registrational study in AITL. Was there any color provided in terms of the two primary endpoints as to what the benchmark would be for either the ORR in patients who carry the cure mutation or the ORR in all patients in the study?

Thanks Tyler.

Thank you and our next question comes from Jay Olson with Oppenheimer. Your line is now open.

Oh, Hey, guys. Congrats on all the progress in new additions to your leadership team.

I wanted to follow up on the positive feedback from FDA Thats your into phase two meeting.

And comments to remain about the Registrational study in.

No.

Was there any color provided.

In terms of.

Two primary endpoints.

As to what the benchmark would be for either the or are in patients who carry the tier mutation or.

Operator: Sure, Jay. This is Troy.

Or are in all patients in the study.

Sure Jay This is Troy thanks for the question.

Troy Edward Wilson: Thanks for the question. So, we now refer to that trial as the trial formerly known as AITL because the T-follicular helper phenotype, including AITL, is a bit of a mouthful. We'll come up with an appropriate name for the trial in the future. But as we mentioned, the design of that trial is consistent with what has been used for other agents that have been approved in PTCL and what would be expected for a level of activity in a second-line setting. We mentioned that each of the two independent objectives has a 9% null hypothesis. So, you know, that's a reasonably low bar.

The.

So we now refer to that trial as the trial formula as they ITCL.

Because the the T. follicular helper phenotype, including LTL is a bit of a mouth mouthful will come up with an appropriate named for the trial in the future, but as we mentioned.

So the design of that trial is consistent with what has been used for other agents that have been approved and PTCL and what would be expected for.

A level of activity in a second line setting.

We mentioned that each of the two independent objectives has a 9% no hypothesis so.

That's a that's a reasonably low bar, we would obviously want to see a higher level of activity. Both in terms of objective response in durability, if we want to displace the existing therapies.

Troy Edward Wilson: We would obviously want to see a higher level of activity, both in terms of objective response and durability, if we want to replace the existing therapies. And you know, we're encouraged because in a patient population that has experienced a median of three priors, so a fourth-line setting, we're seeing a 40-50% response rate with the ability to drive that to 70% in the cure mutant subset and a 40% CR rate. So, there is the potential, we think, to drive a higher level of activity and displace other agents. But specific to your question, those two arms each have a 9% null. And the guidance that we got was that, you know, success eliminating the null hypothesis on either arm, or either endpoint, I should say, I misspoke, would be sufficient to, you know, eliminate the null hypothesis and potentially support an application for accelerated approval. Does that help you?

And we're we're encouraged because in a in a patient population that has experienced a median of three priors. So a fourth line setting we're seeing a.

40% to 50% response rate.

The ability to drive that to 70% in the cure mutant subset and.

And a 40% CR rates. So there is the potential we think to drive a higher level of activity and displace the other agents, but specific to your question. Those two arms each have a 9% NOL and the guidance that we got was that I success, eliminating the no hypothesis on either arm or.

They're endpoint I should say I misspoke would be sufficient to.

To eliminate the no hypothesis and potentially support an application for accelerated approval.

Does that help you.

Troy Edward Wilson: Yes, that's perfect. Thank you. And then, maybe as a follow-up, as you get closer to commercializing TIPI-Farnab, can you talk about how you anticipate the timing of all the various indications you're pursuing and how you want to sequence those potential approvals and manage the life cycle of TIPI-Farnab?

Yes, that's perfect. Thank you.

And then maybe as a follow up as you get closer to commercialization of Tipifarnib.

Can you talk about how you envision the timing.

All the various indications you're pursuing and how you want to sequence those potential approvals and managing the lifecycle of Tipifarnib.

Yeah.

Troy Edward Wilson: So, Jay, that's a great question and probably one that I'm going to give you an unsatisfactory answer to. But let me just say... We are following the science, we are following what we see in the clinic, and we are informed by commercial opportunities. So we chose Ahrefs mutant head and neck and now nodal T-cell lymphomas of the T-follicular helper phenotype as initial indications because they offer, you know, a fast-to-market strategy and you could potentially accelerate approval. We see an opportunity to expand into T-cell lymphomas and potentially other heme malignancies, potentially the opportunity to move into second-line pancreatic cancer. That will obviously take time, but if you look back, you know, several of you on the phone have been following this story almost from the beginning. It wasn't more than a couple of years ago that we couldn't conclusively tell you that TIPI-Farnab was a CXCL12 pathway inhibitor. Now I think we can tell you that we see knockdown, you know, of both the message and the protein in pancreatic stellate cells and encouraging preclinical data and clinical data.

So Jay that's a great question.

And probably one that I'm going to give you an on satisfactory answer too, but let me just say.

We are following the science we are we're following what we see in the clinic and we are informed by the commercial opportunities. So we chose HRS mutant head and neck and now nodal T cell lymphoma as of the T. Follicular helper phenotype as initial indications because they offer.

Fast to market strategy.

And you get the potential for accelerated approval, we see an opportunity to expand.

Expand into T cell lymphoma, as and potentially other heme malignancies potentially the opportunity to move into second line pancreatic cancer that we'll obviously take time, but if you look back of and several of you on the phone if there's been following the story almost from the beginning it wasnt more than a couple of years.

As ago that we did we couldn't conclusively tell you that tipifarnib was the CX IL 12 pathway inhibitor now I think we can tell you that we can tell you that we see knockdown.

Both message and protein in pancreatic Stella itself.

And encouraging preclinical data in clinical data so that that encourages us we are talking in working internally on a strong standalone plan.

Troy Edward Wilson: So that encourages us. We are talking and working internally on a, you know, a strong standalone plan to take Kura forward as well as, you know, considering optionality, you know, by combinations and other things. And we'll give more light to that over time. But at this point, I think we're going to continue to do what has served us well, which is to follow the science and focus very much on excellence.

Take care of forward as well as considering optionality.

No by combinations and other things and we'll we'll give more light to that overtime. At this point I think we're going to continue to do what has served us well, which is follow the science.

And focus very much on execution.

Troy Edward Wilson: That's great. Thank you very much for taking the question. Sure. Thank you.

Great. Thank you very much taking the questions.

Sure Inc.

Operator: And once again, it's star number one to ask a question. Our next question comes from Joseph Patagonist with H.C. Rainwright. Your line is open. Hi guys, this is Pasquale from the line of Joe.

Thank you and once again at Star one to ask a question. Our next question comes from Joseph Pat Again. This was achieved Wainwright. Your line is open.

Hi, guys. This is pasquale from Atlanta true. If you question for me. So my first question. So for the TP funding Trialing minutes, so you'd have to the carcinoma, what kind of update should we expect in Pennsylvania will additional treated patients and also what frequency of interest.

Operator: A few questions for me. So, for the TP funding trial in metastatic ureothelial carcinoma, what kind of updates should we expect in terms of, you know, additional treated patients? And also, what frequency of HRAS mutation are you looking at?

Flotation as you look here.

Yes, well thank you for the question so.

Troy Edward Wilson: Yeah, Pascal, thank you for the question. So that study, that urethelial HRS, that HRS mutant urethelial carcinoma study, is an investigator-sponsored study being conducted at the Samsung Medical Center. It's not under our control. It's actually fully, you know, was designed and was directed by Dr. Park at Samsung. So Dr. Park is the one who will make the determination of how many patients. We guided in the prepared remarks that, you know, we would expect a more complete data set to be presented and or published later this year. Again, this is Dr. Park's study. It's not ours.

Thats study that Urothelial interest that interests mute and Urothelial carcinoma study is an investigator sponsored study being conducted at the Samsung Medical Center.

It's not under our control it's actually.

Fully you know was designed and was directed by Dr. Park at Samsung. So Dr. Park is the one who will make the determination of of how many patients.

We guided in the prepared remarks that we would expect a more complete dataset to be presented and or published later this year again. Its Dr. Park study, it's not ours. So we can guide to that but we can't we can't control it.

Troy Edward Wilson: So we can guide them to that, but we can't control it. You know, but I think we're optimistic if things go well, to see that data presented a bit later this year. In terms of your question about the HRS mutant frequency, you know, estimates vary anywhere from 5 to 15% depending on the literature reference that you look at. So, you know, it's, it's, it's a meaningful percentage of urethelial carcinoma. And I think we'll have more to say once the kind of full data sets are presented, you know, from Dr. Park.

But but I think we're optimistic things go well to see that data presented a bit later this year in terms of your question about the trust mutant frequency.

You know estimates estimates vary anywhere from 5% to 15% depending on the literature referenced that you look at.

So it's it's it's a meaningful percentage of of Urothelial carcinoma, and I think we'll have more to say once the kind of the full datasets been presented.

From from Dr. Park.

Okay. Thank you select short so in other question for me I mean, I saw your IP slide in on your corporate proficiency nice. So I was wondering if you can provide color on deal going novel fun to see transport as need be toast program and specifically what kind of what is this.

Troy Edward Wilson: Thank you so much, Troy. So another question for me, I mean, I saw your IP slide, you know, on your corporate presentation. It's very nice. So I was wondering if you could provide color on the ongoing novel pharmacy transfer rates inhibitors program, and specifically, you know, what kind, what is the status of the preclinical work, any success in identifying potential novel pharmacy transfer rates inhibitors?

There is of the pushing toward any success seating identifying potential local pharmacy transmitters and maybe tours and you know if you have a five for local competition last Thursday piece.

Troy Edward Wilson: Yeah, so you have a few things packed into that question, Pasquale. Let me see if I can unpack them and answer your question.

Yes. So you have if you have a few things packed into that question Pesc, while let me let me see if I can unpack them an answer your question. So.

Troy Edward Wilson: If we take a step back, you know, before we get to the novel FTI, one of the things that I think we've done, you know, we've absolutely delivered on is the ability to unlock the biological insights of farnesyl transferase inhibition. So when we brought this program in from Janssen, it was clear that tipifarnib was active, and it had a reasonable tolerability profile, but there was not a good molecular understanding of what was driving the clinical activity. We now have two sort of major mechanisms. One, HRS mutant solid tumors, and the other CXCL12, you know, hematologic and solid tumors. And we're gonna continue to flesh that story out throughout this year.

If we take a step back.

Before we get to the novel FDI.

One of the things that I think we've done we've absolutely delivered on is the ability to unlock the biological insights of Pharmacell transfer rates inhibition. So when we brought this program in Premier Hanson. It was clear that Tipifarnib was active it was it had a it had a reasonable tolerability profile, but there was not.

Good molecular level understanding of.

Of what was driving the clinical activity, we now have to sort of major mechanisms. One eight tress mutant solid tumors. The other see Axiall 12, hematologic and solid tumors and we're going to continue to flush that story out throughout this year.

Troy Edward Wilson: You know, I don't wanna say too much, but we really view ourselves as the leader in farnesyl transferase inhibition, and that is, understanding the molecular mechanisms, understanding opportunities as monotherapies, understanding rational combinations. And we've been very successful both in the U.S. and now increasingly outside the U.S. at getting patent offices to issue fairly broad patents covering not only tipifarnib but any farnesyl And that's because, you know, we did what no company working previously was able to do, and that was to assign the molecular target. With that, you know, and that was that it took, as you can imagine, kind of an alignment of planets to get that right. But here we are.

I don't want to say too much, but we really view ourselves as the leader in Farnesene Transferees inhibition and that is understanding the molecular mechanisms understanding opportunities as a monotherapy understanding rational combinations and we've been very successful both in the us and now increasingly X.

US at getting patent offices to issue.

You know fairly broad patents covering not only tipifarnib, but any farnesene transfer ace inhibitor in certain settings, and that's because we did what no company working previously was able to do and that was to assign the molecular targets.

With that that was that that took as you can imagine kind of an alignment of planets to get that right, but here we are.

Troy Edward Wilson: Now we're at a point where we understand the opportunity, we understand the farnesylated targets, and there are things we think we can improve upon, even with a drug that is as well-positioned as tipifarnib. So we started a second generation compound. I've made this reference before, you know; one of the analogies I make is to former Celgene that worked with initially thalidomide, and then Revlimid, and then pomalidomide and simultaneously worked out the Imid biology and developed a very robust franchise. We'd like to be in a position to do something similar in farnesyl transferase inhibition. I can't really speak to where the program is at, but you know, this is, we obviously have crystal structures, you know, we have a number of highly potent compounds, both ours and others. And I think it's a good opportunity for a very efficient drug discovery effort. And I hope that we'll have something more to say, you know, either later this year or early next year.

Now we're at a point, where we understand the opportunity we understand the pharma slated targets and there are things. We think we can improve upon even with a drug that is as well positioned as tipifarnib. So we started a second generation compound I've made this reference before.

One of the analogies I make is too.

Formerly Celgene that worked with initially solidified and then Revlimid and then Pomalidomide.

And simultaneously worked out the amid biology and developed a very robust.

Robust franchise, we'd like to be in a position to do something similar in foreign steel transferase inhibition I can't really speak to where the program has that but this is.

We obviously have crystal structures, we have a number of highly potent compounds, both ours and others and I think it's a good opportunity for a very efficient drug discovery effort and I hope that we'll have something more to say either later this year early next year.

Troy Edward Wilson: That's very helpful. Thank you for the additional call. Last question on my end: So what kind of update should we expect for the TP finding trial in chronic myelomonocytic leukemia?

That's helpful. Thank you for any additional color last question on land. So what kind of update should we expect for the TP funding trial incremental meal mobile sleepiq leukemia.

Sure, Yes, thats good question so.

Troy Edward Wilson: Yeah, that's a good question. If we take a step back, we initially reported data in CMML that one, you know, we had an initial phase two study where we were looking to exclude KRAS and NRAS mutant patients from those patients with CMML because it had been established that KRAS and NRAS were not driver oncogenes that could be addressed with tipifarinib or a farnesyl That study was successful. We then, once we identified the molecular insight of the CXCL12-CXCR4 interaction, we took a look at T-cell lymphoma, you know, at additional lymphomas as well as into leukemias and thought, you know, should we be enriching on the basis of the CXCL12 pathway and continued to run the study, but not looking at NRAS or at KRAS and So we'll provide an update on that study. You know, our expectation is, you know, sometime, we hope, kind of mid-year to the second half of

If we if we take a step back.

We initially reported data in CML that one we had an initial phase two study, where we were looking to exclude K rasen end rest mutant patients from from those patients with CML because it had been established that KRS and then Ras we're not driver on.

Good genes that could be addressed with tipifarnib reforms will transfer ace inhibitor as a monotherapy that study was successful.

We then once we identified the molecular insight of the C. Axiall 12, CXC. Our four interaction we took a look at T cell lymphoma.

I had additional lymphomas as well as into leukemias and thought you know should we be enriching on the basis of the C. Axiall 12 pathway and continued to run the study, but not looking at end Ras KRS and then Ras but at sea Axiall 12, Unsexy. Our four so we'll provide an update on that study are.

Expectation is sometime we hope kind of mid mid year to second half of the year.

Troy Edward Wilson: Perfect. Thank you so much, Troy, and congratulations on the progress. My pleasure. Thank you, and I'm not showing any further questions. I'd like to turn the call back to Troy Wilson for any further remarks.

Perfect. Thank you so much Troy congrats on deposits.

My pleasure.

Thank you I'm not showing any further questions I'd like to turn the call back to Troy Wilson for any further remarks.

Troy Edward Wilson: Okay, thank you, operator. And thank you all, once again, for participating in our call today. We're going to be at a number of upcoming investor conferences, beginning with SVB Lyric tomorrow in New York. We'll look forward to seeing many of you there. And in the meantime, if you have any questions, please feel free to contact Pete, Mark, or myself. Thank you, and have a good evening, everyone.

Okay. Thank you operator, and thank you all once again for participating in our call today, we're going to be at a number of upcoming investor conferences, beginning with SBB Leerink Tomorrow in New York, We'll look forward to seeing many of you there and in the meantime, if you have any questions. Please feel free to contact Pete Maher.

Mark or myself, thank you and have a good evening everyone.

Operator: Ladies and gentlemen, this concludes today's conference.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.

Operator: This concludes today's conference call. Thank you for your participation. You may now disconnect.

Operator: BF-WATCH TV 2021

Okay.

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