Q3 2021 Kura Oncology Inc Earnings Call

Please standby we're about to begin.

Operator: Please stand by; we're about to begin.

Good day and welcome to the Cura oncology three Q conference call. Today's call is being recorded I'll now turn the call over to Pete de Spain. Please go ahead Sir.

Operator: Good day and welcome to the Cura Oncology 3Q conference call. Today's call is being recorded. I'll now turn the call over to you.

Operator: I'll now turn the call over to Pete Dispain. Please go ahead.

Thank you Paula good afternoon, and welcome to Curl oncology third quarter 2021 conference call. Joining me on the call are Dr. Troy Wilson, our President and Chief Executive Officer, and Dr. Marc Grasso, Our Chief Financial Officer, and Chief Business Officer, Dr. Steven Dale, Our Chief Medical Officer, Kirsten flowers, our chief commercial officer.

Pete De Spain: Thank you, Paula. Good afternoon, and welcome to Kura Oncology's third quarter 2021 conference call. Joining me on the call are Dr. Troy Wilson, our president and chief executive officer, and Dr. Mark Grasso, our chief financial officer and chief business officer.

Pete De Spain: Dr. Steven Dale, our chief medical officer, Kirsten Flowers, our chief commercial officer, and Kathy Ford, our chief operating officer, are 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 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.

And Kathy Ford, our Chief operating officer are 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 expectations.

Such statements represent managements judgment as of today and May involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to <unk> filings with the SEC, which are available from the SEC or on the current oncology website for information concerning risk factors that could affect the company with that I will now turn the.

Pete De Spain: Please refer to Kuro'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 will now turn the call over to Dr. Troy Wilson, president and CEO of Curra Oncology. Thank you, Pete, and thank you all for joining us this afternoon.

Call over to Dr. Troy Wilson, President and CEO of Kura oncology.

Thank you Pete and thank you all for joining US. This afternoon I'm pleased by the progress our team has made over the past quarter highlighted by accelerated enrollment in the phase one expansion cohorts for <unk> 539.

Troy Edward Wilson: I'm pleased by the progress our team has made over the past quarter, highlighted by accelerated enrollment in the Phase 1B expansion cohorts for KO539, preclinical data highlighting the molecular mechanisms of activity for KO539 and its potential for synergistic combination with Venetaclax, First, Clinical Site Activated in the Phase 1-2 trial of Tipifarnib plus El Pelisib in head and exquemis As an organization, we remain focused on our three main programs.

Preclinical data highlighting the molecular mechanisms of activity for <unk>, $5 39, and its potential for synergistic combination with vanilla clocks.

First clinical site activated in a phase one two trial of <unk>, plus <unk> in head and neck squamous cell carcinoma, and ongoing IND, enabling studies for <unk> 2008 O six.

As an organization we remain focused on our three main programs, our menin inhibitor <unk> $5 39 in acute leukemia.

Troy Edward Wilson: Our Mennon inhibitor, K.O.539, in acute leukemia, our Farnasil-transferase inhibitor, Tippy Farnib and Hennin-X in squamous cell carcinomas, and our next generation Farnesil transferase inhibitor, KO-2806, in solid tumors. We believe these programs have the potential to create significant value for patients, healthcare providers, and shareholders, and we believe Now, let's take a closer look at the progress within each of the programs, beginning with K-0539.

Farnesol transfer ace inhibitor to be farther than head and neck squamous cell carcinomas and our next generation Farnesol transfer Ace inhibitor <unk> hundred 28, six in solid tumors.

We believe these programs have the potential to create significant value for patients healthcare providers and shareholders and we believe we have the experienced leadership and financial resources to deliver that value.

Now, let's take a closer look at the progress within each of the programs beginning with <unk> 39.

We've completed the phase one dose escalation study of $5 39, which demonstrated encouraging single agent activity in an all comer population of patients with relapsed <unk> refractory AML, including those with N. P. M. One mutations and Kmt to a rearrangement.

Troy Edward Wilson: We've completed the Phase 1A dose escalation study of 539, which demonstrated encouraging single-agent activity in an all-comer population of patients with relapsed and or refractory AML, including those with NPM 1 mutations and KMT2A rearrangements. KO539 also showed a favorable safety and tolerability profile, notably with no evidence of QTC prolongation. We intend to conduct a comprehensive clinical development plan for KL539 both as monotherapy and in combination. A key step is determination of a recommended phase two dose, which is the goal of our ongoing Phase 1B study.

539 also showed a favorable safety and tolerability profile, notably with no evidence of Q T C prolongation.

We intend to conduct a comprehensive clinical development plan for <unk> 539, both as a monotherapy and in combination a key step is determination of a recommended phase two dose which is the goal of our ongoing phase one B study. We're currently enrolling two expansion cohorts, a lower dose 200 milligrams and a higher dose.

Troy Edward Wilson: We're currently enrolling two expansion cohorts, a lower dose of 200 milligrams and a higher dose of 600 milligrams, and each cohort is comprised of patients with NPM1 mutant or KMT2 rearranged, relapsed, and or refractory AML. The doses being evaluated in the Phase 1B studies were selected based on the clinical activity, safety, and tolerability demonstrated in the Phase 1A

<unk> 600 milligrams in each cohort is comprised of patients with N. P. M. One mutant or Kmt two rearranged relapsed <unk> refractory AML.

The doses being evaluated in a phase one b were selected based on the clinical activity safety and Tolerability demonstrated in the phase <unk> study.

We continue to be encouraged by the preliminary results from the phase one B study, thus far with evidence of activity at both doses and a favorable safety and Tolerability profile. We're also encouraged by the enthusiasm of our investigators with approximately half of an estimated 40 global sites now actively screening patients for enrollment in the study.

Troy Edward Wilson: We continue to be encouraged by the preliminary results from the Phase 1B study thus far, with evidence of activity at both doses and a favorable safety and tolerability profile. We're also encouraged by the enthusiasm of our investigators, with approximately half of an estimated 40 global sites now actively screening patients for enrollment in the study. We continue to aggressively add sites in the U.S. and Europe in anticipation of the phase two portion of the study, and we maintain our enrollment guidance of 12 evaluable patients in each cohort of the Phase 1B study by the first quarter of 2022.

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We continue to aggressively add sites in the U S and Europe in anticipation of the phase II portion of the study and we maintain our enrollment guidance of 12 evaluable patients in each cohort of the phase <unk> study by the first quarter of 2022.

Once enrolled we will assess the patients in each cohort for safety and Tolerability pharmacokinetics and efficacy to determine the recommended phase two dose.

Troy Edward Wilson: Once enrolled, we will assess the patients in each cohort for safety and tolerability, pharmacokinetics, and efficacy to determine the recommended Phase 2 dose. The study protocol also gives us the flexibility to enroll up to 30 patients in the selected cohort.

The study protocol also gives us flexibility to enroll up to 30 patients in the selected cohort. This enables us to continue enrolling patients in the phase one B study at the recommended phase two dose while we transition into a subsequent registration directed portion of the study.

Troy Edward Wilson: This enables us to continue enrolling patients in the Phase 1B study at the recommended phase two dose while we transition into a subsequent registration-directed portion of the study. Importantly, we believe data from all patients treated at the recommended phase two dose have the potential to contribute to the registrational patient population. Thus, our Phase 1B study not only helps us to refine the selection of a recommended phase two dose, but it enables us to start our path toward registration while maintaining an aggressive development timeline for the program.

Importantly, we believe data from all patients treated at the recommended phase two dose has potential to contribute to the registrational patient population. Thus our phase one b study not only helps us to refine selection of a recommended phase two dose, but it enables us to start our path toward registration, while maintaining an aggressive.

Ziv development timeline for the program.

We intend to provide a more comprehensive update on the phase one eighth of the phase one study, including results from the phase <unk> and the phase one b at a future medical meeting pending determination of the recommended phase two dose.

Troy Edward Wilson: We intend to provide a more comprehensive update on the Phase 1 study, including results from the Phase 1A and the Phase 1B, at a future medical meeting pending determination of the recommended Phase 2 dose. Based on our progress and the totality of the clinical and preclinical data to date, we continue to believe KO539 has the potential to be both a first in class and a best in class menin inhibitor. As such, we're designing a development strategy that builds on the potential to register K0539 as a monotherapy while giving us flexibility to get to larger opportunities in combination more quickly, including earlier lines of therapy.Efforts are already underway to support some of these additional development activities.

Based on our progress and the totality of the clinical and preclinical data to date, we continue to believe K O 539 has potential to be both a first in class and best in class Menin inhibitor.

As such we are designing a development strategy that builds on the potential to register K O <unk> 39, as a monotherapy, while giving us flexibility to get to larger opportunities in combination more quickly, including earlier lines of therapy efforts are already underway to support some of these additional development activities.

For example, encouraging preclinical data has been generated through our research collaboration with Dr. Rick Appeal Bhalla at M. D. Anderson, highlighting the molecular mechanisms of K O $5 39, and its potential for synergistic activity in combination with vanilla clocks in K M. T. Two rearranged and N P. M. One mutant AML models.

Troy Edward Wilson: For example, encouraging preclinical data have been generated through a research collaboration with Dr. Kapil Bala at MD Anderson highlighting the molecular mechanisms of KO539 and its potential for synergistic activity in combination with Benetaclax in KMT2 rearranged and NPM1 mutant AML models. These data have been accepted for presentation at the upcoming American Society of Hematology Annual Meeting. The abstract was published earlier today and is now available on the Ash Foundation website.

These data have been accepted for presentation at the upcoming American Society of Hematology annual meeting the abstract was published earlier today and is now available on the Ash website.

We look forward to Dr. <unk> presentation next month and to sharing our progress with you as we continue to drive toward a recommended phase two dose for <unk> hundred 39 next quarter.

Troy Edward Wilson: We look forward to Dr. Bala's presentation next month and to sharing our progress with you as we continue to drive toward a recommended phase two dose for K0539 next quarter. Turning our attention now to Farnesil Transphrase, we continue to view Farnesil Transprace inhibition as a potentially valuable therapeutic and commercial franchise, one with the potential to deliver multiple opportunities in oncology. For example, earlier today, an abstract was published with the final results from a phase two study of tipharinib in patients with relapsed or refractory peripheral T-cell lymphoma.

Turning our attention now to Farnesol transfer as we continue to view Farnesol transfer ace inhibition as a potentially valuable therapeutic and commercial franchise, one with potential to deliver multiple opportunities in oncology for.

For example earlier today, an abstract was published with the final results from a phase two study of <unk> in patients with relapsed or refractory peripheral T cell lymphoma.

Although we paused continued development of <unk> in T cell lymphoma in early 2020 to focus on our programs in head and neck squamous cell carcinoma in AML. The phase II trial continue the final results will be presented by Dr. Thomas Witzig Hematologist at Mayo clinic in the study's lead investigator in an oral presentation at.

Troy Edward Wilson: Although we paused the continued development of tipfarinib in T-cell lymphoma in early 2020 to focus on our programs in head and xquimicicill carcinoma and AML, the phase two trial continued. The final results will be presented by Dr. Thomas Witzig, haematologist at Mayo Clinic and the study's lead investigator, in an oral presentation at Ash. This abstract can also be found on the Ash website.

Dash. This abstract can also be found on the ash website.

Clinical benefit demonstrated in patients with certain subtypes of T cell lymphoma, including an overall response rate of 56, 3% and a median overall survival of 32.8 months in patients with NGL Immunoblastic T cell lymphoma underscore the potential to target Farnesol transfer ace to drive clinical benefit in patients.

Troy Edward Wilson: The clinical benefit demonstrated in patients with certain subtypes of T-cell lymphoma, including an overall response rate of 56.3% and a median overall survival of 32.8 months in patients with NGO-immunoblastic T-cell lymphoma, underscores the potential to target Farnesil transfraise to drive clinical benefit in patients. As most of you know, our most advanced effort with Tipifarnib is focused on patients with head and neck squamous cell carcinomas, or HNSC, which carry mutations in the HRS genes.

As most of you know.

Our most advanced effort with Tippi foreign are as focused on patients with head and neck squamous cell carcinoma is our H N S. C C, which carry mutations in the HRS gene J P. Foreign or has been awarded breakthrough therapy designation from FDA for the treatment of patients with recurrent or metastatic <unk> mutant H N. S. C. C. The breakthrough therapy designation was based upon data.

Troy Edward Wilson: Tipifarnib has been awarded breakthrough therapy designation from FDA for the treatment of patients with recurrent or metastatic, H-R-S mutant HNSCC. The breakthrough therapy designation was based on data from our Phase 2 run HN trial, which was published earlier this year in the Journal of Clinical Oncology. We continue to be motivated by these data and remain focused on our AMHN registration-directed trial of TIPPFARNM as a monotherapy in patients with H-R-S-muton HNSCCC.

From our phase II run HN trial, which was published earlier this year in the journal of clinical oncology, we continue to be motivated by these data and remain focused on our aim HN registration directed trial is tippy Farnham as a monotherapy with in patients with Hs meet an H N S. C C.

In addition to addressing an urgent unmet need for patients we believe the opportunity for typify in HRS mutant H N. S. C. C provides a beachhead to the development of rational combinations and the expansion to larger genetic subsets.

Troy Edward Wilson: In addition to addressing an urgent unmet need for patients, we believe the opportunity for TIPI Farnib in H-R-S-Muton HNSCC provides a beachhead for the development of rational combinations and the expansion to larger genetic subsets. Just last month, a review paper was published in the journal Cancers, highlighting the rationale and preclinical and clinical data that support the potential for pharnasol transprice inhibitors in combination regimens in squamous cell carcinoma. Among these potential combinations, we've identified the combination of tippy farinib and a PI3-Kinae-S alpha inhibitor as a priority. Our pre-clinical data suggests that H-RAS and PI3-Kinae Alpha are codependent oncogenes in HNSCC, and that combining tippifarnib with a PI3-Kinae-Salf inhibitor has the potential to provide meaningfully better antitumor activity relative to inhibiting either target alone.

Last month, a review paper was published in the journal cancers, highlighting the rationale and preclinical and clinical data that support the potential for Farnesol transfer Ace inhibitors in combination regimens in squamous cell carcinomas. Among these potential combinations, we've identified as a priority the combination of tip. Your foreign had been a P. S. We kind of sell.

<unk> inhibitor, our preclinical data suggests that a trash and P. S. <unk> kinase Alpha are codependent, oncogene, and H N S. C C and that combining <unk> with a P. S. <unk> kinase Delta inhibitor has potential to provide meaningfully better antitumor activity relative to inhibiting either target a low.

We believe this combination has the potential to increase the total addressable population for <unk> to as much as 50% of patients with H N S. C C.

Troy Edward Wilson: We believe this combination has the potential to increase the total addressable population for TIPIFARNib to as much as 50% of patients with HNSCC. In this past quarter, we announced a clinical collaboration with Novartis to evaluate the combination of Tipifarnib and the PI3-Kinib alpha inhibitor alpelisib in patients with HNSCC. Al-Pelisib is approved to treat patients with Pick 3CA mutant breast cancer, and it has demonstrated encouraging evidence of clinical activity in patients with HNSCC. We're now actively preparing for a Phase 1-2 study of Tipi-Farnib in combination with al-Pelisib in HNSCC, which we call The current trial?

This past quarter, we announced a clinical collaboration with Novartis to evaluate the combination of <unk> and the <unk> kinase Alpha inhibitor <unk> in patients with H N. S. C. C. L. Palisade is approved to treat patients with pick three C. A mutant breast cancer and it has demonstrated encouraging evidence of clinical activity.

In patients with H N S. C. C. We're now actively preparing for a phase one two study of <unk> in combination without palisade N H N S C C, which we call the current trial.

The initial cohort will include patients who have picked three C. A dependent H N. S. C. C. These patients can be identified using next generation sequencing, which should allow us to identify a recommended phase two dose for the combination. We've now activated the first clinical site and we're on track to begin dosing patients in the current trial by the end of this year.

Troy Edward Wilson: The initial cohort will include patients who have PIC3CA dependent HNSCC. These patients can be identified using next-generation sequencing, which should allow us to identify a recommended phase two dose for the combination. We've now activated the first clinical site, and we're on track to begin dosing patients in the current trial by the end of this year. Meanwhile, through our own internal efforts and our network of academic collaborators, we've identified some exciting opportunities for Farnesil Transphrase inhibitors in combination with other targeted therapies in large solid tumor indications.

Meanwhile, through our own internal efforts and our network of academic collaborators.

We've identified some exciting opportunities for Farnesol transfer Ace inhibitors in combination with other targeted therapies in large solid tumor indications opportunities that we believe represent significant potential value creation.

Troy Edward Wilson: Opportunities that we believe represent significant potential value creation. Last quarter, we nominated K0-2806 as the lead development candidate in our next-generation Farnacil Transverse Inhibitor Program, a compound with improved potency, pharmacokinetic, and physical chemical properties relative to TIPI Farnum.

Last quarter, we nominated K O 28 O six as the lead development candidates in our next generation Farnesol transfer Ace inhibitor program.

Within our compound with improved potency pharmacokinetic and physical chemical properties relative to typify it at our.

Our next Gen F. T. I program is designed to target innovative biology and to address large solid tumor indications of high unmet need through rational combinations with a focus on delaying the onset of drug resistance.

Troy Edward Wilson: Our NextGen FTI program is designed to target innovative biology and to address large solid tumor indications of high unmet need through rational combinations with a focus on delaying the onset of drug resistance. We're very excited about this emerging opportunity, and we look forward to sharing more information in the months ahead. With that, I'll now turn the call over to Mark Grasso for a discussion of our financial results. Thank you, Troy.

Excited about this emerging opportunity and we look forward to sharing more information in the months ahead with that I'll now turn the call over to Marc Grasso for a discussion of our financial results. Thank you Troy and good afternoon, everyone. I'll provide a brief overview of our financial results for the third quarter 2021, along with reiterating our guidance for the full year two.

Mark Grasso: And good afternoon, everyone. I'll provide a brief overview of our financial results for the third quarter of 2021, along with reiterating our guidance for the full year 2021. I invite you to review our 10Q file today for more detailed discussion. Research and development expenses for the third quarter of 2021 were $22.4 million, compared to $16.6 million for the third quarter of 2020. The increase in R&D expenses was primarily due to increases in clinical trial costs, development, and manufacturing activities related to our KO539 program, clinical trial costs related to our registration-directed trial of TIPA marnet, non-cash share-based compensation, personnel costs, and other expenses.

'twenty one.

I invite you to review our 10-Q filed today for a more detailed discussion.

Research and development expenses for the third quarter of 2021, or $22 4 million compared to $16 6 million for the third quarter 2020.

The increase in R&D expenses was primarily due to increases in clinical trial costs development and manufacturing activities related to our Q3 nine program clinical trial costs related to our registration directed trial to record a noncash share based compensation personnel costs and other expenses Jim.

General and administrative expenses for the third quarter of 2021 were $11 $3 million compared to $7 $6 million for the third quarter of 2020.

Mark Grasso: General and administrative expenses for the third quarter of 2021 were $11.3 million, compared to $7.6 million for the third quarter of 2020. The increase in G&A expenses was primarily due to increases in personal costs, professional fees, and non-cashare-based compensation.

The increase in G&A expenses was primarily due to increases in personnel costs professional fees and noncash share based compensation.

Net loss for the third quarter of 2021 was $33 $4 million or <unk> 50 per share compared to a net loss of $23 $8 million or <unk> 42 per share for the third quarter of 2020.

Mark Grasso: The net loss for the third quarter of 2021 was $33.4 million, or 50 cents per share, compared to a net loss of $23.8 million, or 42 cents per share, for the third quarter of 2020. As of September 30, 2021, we had cash, cash equivalents, and short-term investments of $543.4 million, compared with $633.3 million as of December 31st, 2020. We continue to anticipate our operating expenses for the full year 2021 to be in the range of $130 million to $140 million.

As of September 32021, we had cash cash equivalents and short term investments of $543 4 million.

Compared with $633 $3 million as of December 31, 2020.

We continue to anticipate our operating expenses for the full year 2021 to be in the range of $130 million to a $140 million.

We continue to expect our net cash used in operating activities for the full year 2021 to be in the range of 105 million to $115 million.

Based on our current plans, we continue to believe that our cash cash equivalents and short term investments will be sufficient to fund current operations into 2024 with that I will now turn the call back over to Troy.

Mark Grasso: We continue to expect our net cash use in operating activities for the full year 2021 to be in the range of 105 million to 150 million. Based on our current plans, we continue to believe that our cash, cash equivalents, and short-term investments will be sufficient to fund current operations into 2024.

Thanks, Mark before we jump into the question and answer session, Let me lay out our anticipated upcoming milestones.

Dose the first patient in the current phase one two study of <unk> in combination with <unk> by the end of 2021.

Complete enrollment of 24 evaluable patients in the comment Zero-zero, one phase one expansion cohorts by the first quarter of 2022.

Operator: With that, I will now turn the call back over to Mark. Before we jump into the question and answer session, let me lay out our anticipated upcoming milestones. Dose the first patient in the current Phase 1-2 study of Tipifarnib in combination with Alpelisib by the end of 2021. Complete enrollment of 24 valuable patients in the Comet-001, Phase 1B Expansion cohorts by the first quarter of 2022. Determine the recommended phase two dose of K0539 by the first quarter of 2022 and submit an I&D application for KO2806 by the end of 2022.

Determined the recommended phase two dose of <unk> $5 39 by the first quarter of 2022.

And submit an IND application for K O 28, or six by the end of 2022.

With that operator, we're now ready for questions.

Thank you to signal for a question. Please press star one on your telephone keypad also if you are using a speaker phone. Please make sure that your mute button is turned off to allow your signal to reach our equipment.

Once again it is star one at this time for questions and we will pause to give everyone the opportunity to signal.

We will take our first question from Jonathan Chang with SBB Leerink.

Operator: With that operator, we're now ready for questions. Thank you for signaling for a question. Please press star one on your telephone keypad. Also, if you are using a speakerphone, please make sure that your mute button is turned off to allow your signals.

Hi, guys. Thanks for taking my questions. First question can you provide any more granular color on comments in the press release.

Hitting evidence of activity at both dose and a favorable safety and Tolerability profile.

Operator: to reach our equipment. Once again, it is Star 1 at this time for questions, and we'll pause to give everyone the opportunity.

Okay.

Yeah.

Jonathan.

As we said we're enrolling both of the lower dose cohort in the higher dose cohort.

And we are encouraged by what we're seeing in terms of clinical activity.

Operator: and we'll pause to give everyone the opportunity to signal. We'll take our first question from Jonathan Chang, with SVB Laring.

Unfortunately at this point given that this is a a phase one b study, that's where patients are randomized has to dose we can't be any more granular at this point, but I think we're encouraged very encouraged by the direction that were going by enrollment and we look forward to providing additional qualitative updates.

Jonathan Chang: Hi guys, thanks for taking my questions. First question, can you provide any more granular detail on comments and a press release indicating evidence of activity at both doses and a favorable safety and tolerability profile?

Troy Edward Wilson: Yeah, Jonathan, as we said, we're enrolling both the lower dose cohort and the higher dose cohort. We are encouraged by what we're seeing in terms of clinical activity. Unfortunately, at this point, given that this is a phase 1B study where patients are randomized as to dose, we can't be any more granular at this point, but I think we're very encouraged by the direction that we're going, by enrollment, and we look forward to providing additional qualitative updates. We also think, Jonathan, as we said in the prepared remarks, that we're on track to hit the goals of full enrollment and determination of the recommended phase two dose by the first quarter of 2020.

We also think Jonathan as we said in the prepared remarks that we're on track to hit the goals of full enrollment and determination of the recommended phase II dose by the first quarter of 2022.

Got it understood.

Second question what is your latest thinking on whether kao 539, or other menin inhibitors, I will show comparable or different levels of activity.

<unk> mutant patients versus Pan P to a rearranged patients.

Troy Edward Wilson: Got it, understood. Second question, what is your latest thinking on whether K0539 or other menin inhibitors will show comparable or different levels of activity in NPM1 mutant patients versus KMT2A rearranged patients? Okay.

Sure. Thanks for that Jonathan Let me just press pause I realized I neglected to answer the safety and Tolerability question and your last question too.

To this point, we've seen we continue to see what we're characterizing as a very favorable safety and Tolerability profile.

Troy Edward Wilson: Sure, thanks for that. Jonathan, let me just press pause.

Very much consistent with what was seen in the phase <unk>. So.

Troy Edward Wilson: I realized I neglected to answer the safety and tolerability question in your last question. To this point, we've seen and continue to see what we're characterizing as a very favorable safety and tolerability profile, very much consistent with what was seen in Phase 1A. So I just wanted to, I neglected to mention that in my last answer. With regard to activity against two genetic subtypes, we haven't seen any, you know, clinically or preclinically, actually, any basis for believing that there is a difference in dose between those two genetic subtypes.

So I just wanted I had neglected to mention that in my last answer with regard to activity against two genetic subtypes.

We haven't seen any.

Clinically or pre clinically actually.

Any basis for believing that there is a difference in dose between those two genetic subtypes.

And you know nothing that would would convince us that those two populations I should respond any differently I think whether you're looking at our trial or at the trial of our you know one of our competitors were talking about small numbers very small numbers and a response here or there can can skew the balance at this point.

Troy Edward Wilson: And, you know, nothing that would convince us that those two populations should respond any differently. I think whether you're looking at our trial or at the trial of one of our competitors, we're talking about small numbers, very small numbers, and, you know, you know, a response here or there can skew the balance. At this point, you know, we believe, based on what we have today, we believe that the recommended Phase 2 dose that we determined in Phase 1B will be sufficient to support activity, safety, and tolerability, both in the KMT2A and the NPM one mutant population.

We believe based on what we have today, we believe that the recommended phase two dose that we determine in the phase one b will be sufficient to support our activity safety and tolerability. Both in the K M. T. Two a N a N P M <unk> mutant populations.

Understood and just last question from me could you guys get a chance to review the competitor Ash abstracts today.

Troy Edward Wilson: Okay. And just last question from me: did you guys get a chance to review the competitor Ash Abstracts today? And if so, I'd love to hear thoughts on any learnings that you got from that as it applies to the men in space. Thank you.

So I'd love to hear your thoughts on any learnings that you got from that.

The price of the minutes space. Thank you.

Yes.

Yeah. Thanks. Thanks for the question. So yeah, we did see we did see the ash abstract from from one of our competitors I would say.

Troy Edward Wilson: Yeah, thanks for the question. So yeah, we did see the ash abstract from one of our competitors. I would say... We continue to be very encouraged by the clinical activity that they're seeing, both in the KMT2A and in the NPM1 mutant populations. They're seeing a very encouraging response rate. They're seeing a rate of CRCRH that's perhaps on the lower bound of the guidance that we've given of 20 to 30 percent. But I'll just remind everybody, you know; it's early.

We continue to be very encouraged by the clinical activity that they're seeing both in the K M T. Two way and in the N P. M. One.

Mutant populations.

You know, they're seeing they're seeing a very.

Very encouraging response rate, they're seeing a rate of CRC, our age thats, perhaps on the lower bound of the guidance that we've given of 20% to 30%, but I'll just remind everybody you know it's early both.

Troy Edward Wilson: Both, you know, these data are being gathered, and they're maturing in real time. We continue to believe, Jonathan, that there is potentially an opportunity to register at least 539 in both NPM1 and KMT2A. What I think we didn't see, and this isn't a criticism, is we didn't see any clarity from that abstract in terms of the recommended phase two dose. So, at least as far as when that abstract was submitted, you know, they're very much where we are, or they were where we are, which is determination of the right going forward dose.

These data are being gathered and they're maturing in real time, we continue to believe Jonathan that there's potentially an opportunity to register amenity Register at least $5 39 in both.

N P M, one and Kmt to a what I think we didn't see and this isn't a criticism. It is we didn't see clarity from that abstract in terms of the recommended phase two dose so at least as far as when that abstract was submitted.

They're very much where we are or where they were where we are which is determination of the REIT going forward dose.

And I think.

Troy Edward Wilson: And I think, you know, as far as what we're doing with KO539, our hope and expectation is that, next year, when we show the full phase one data, you'll have a very clear picture of the safety and tolerability and the efficacy at the specific phase two dose. And real clarity as to how that reads through into an ultimate registration-enabling study as a monotherapy or how it will work in combination with other agents in earlier lines of therapy? That's, I think, the thing that we found missing, and perhaps they'll provide more color, you know, on that in the days and weeks ahead.

As far as what we're doing with Kale $5 39 or.

Our hope and expectation you know next year when we show the full phase one data is you'll have a very clear picture on the safety and Tolerability and the efficacy at the at the specific recommended phase two dose and real clarity as to then how does that read through into an ultimate registration enabling.

He is a monotherapy or how will it play in combination with other agents in earlier lines of therapy. That's that's that's I think the thing that we've found missing and perhaps they'll provide more color.

On that in the days and weeks ahead.

Got it thank you.

Sure.

Moving on we'll go to Thiago Falck with credit Suisse.

Operator: Moving on, we'll go to Tiago Fouth with credits. Hey, thanks for thinking up a question. Perhaps just a follow-up

Alright, Thanks for taking the question, perhaps just a follow up on your competitors update they did provide some early duration of response data for patients who achieved CR, sorry, H, which seems to be lower than some other targeted agents, but again I wanted to get your thoughts on how to interpret those data in the context of this spritzer.

Tiago Fouth: Your competitors update, they did provide some early duration of response data for patients that achieved CRCRH, which seems to be lower than some other targeted agents, but again, I wanted to get your thoughts on how to interpret those data in the context of this particular relapse-refractory patient population and what you think is a reasonable benchmark for that metric specifically. And then a quick follow-up on just on TP 4-Nab. I know it's difficult to predict enrollment.

Nicole are relapsed refractory patient population.

And what you think is a is a reasonable benchmark for for that metric specifically.

And then just a quick follow up on just want to before now, but I know it's difficult to do.

To predict enrollment before the aim HN trial, just any updates there on when we could see some data would be helpful. Thanks.

Tiago Fouth: for the AIMHN trial, just any updates there on when we've

Tiago Fouth: on when we could see some data would be helpful. Thanks.

Sure so.

Troy Edward Wilson: Sure, so let's take those questions in Turrentiago. So on the bar, the hurdle, if you will, for median duration of response, we continue to guide that we think it's approximately six months. If you look at the data from that abstract from our competitor, they still have 13 patients on study. In our experience, that duration of response is likely to get longer. You know, again, I will refer you to them to speak to their data, but I wouldn't get overly exercised about that duration of response.

Let's take those questions in turn Thiago so on the.

On.

The bar the hurdle if you will for median duration of response, we continue to guide that we think it's approximately six months.

The if you look at the data from from that abstract from our competitor. They still have 13 patients on study.

In our experience that duration of response is likely to get longer.

Again, I will refer you to them participate to their data, but I wouldn't get overly exercised about that that duration of response.

It's also you know it's very early days and I just want to stress the point that I I stress to Jonathan before.

Troy Edward Wilson: It's also, you know, it's very early days, and I just want to stress a point that I stressed to Jonathan before: this was all done in the context of dose optimization, right? So, I think the needle is deflecting in the right direction. Clearly, you want to see, you know, longer duration is always better, but I think we, you know, on balance, we came away with the impression that the Syndex update was a good update. It was an encouraging update.

This was all done in the context of dose optimization right. So.

I think the needle is deflecting in the right direction.

Clearly you want to see longer duration is always better but I think we you know on balance we came away I think this index update was a good update it was an encouraging update.

In terms of the enrollment around aim HN.

Troy Edward Wilson: In terms of the enrollment around AMHN, we're not at a point, Tiago, to give you an update on that. That study continues to enroll patients. We are, as we indicated in the prepared remarks. We should very imminently be dosing the first patients in the current study, and we've taken pains to make sure that the current study doesn't cannibalize the AMHN study. That's part of why we're starting with the PIC3CA mutant population, which by any estimate is, you know, anywhere from three to five times larger than the H.R.S.

At a point Thiago to to give you an update on that that study continues to enroll patients.

We are as we had indicated in the prepared remarks, we should very imminently be dosing. The first patients in current and we've taken pains to make sure that that the current study doesn't cannibalize. The aim HN study that's part of why we're starting in the pick three C. A mutant population, which by any estimate is.

You know anywhere from three to five times larger than the HRS mutant. So aim is ongoing current we'll start here.

Troy Edward Wilson: Mutant. So the aim is ongoing. Current will start here, certainly before the end of the year. And I think that, you know, that's going to build on the clinical data that we've already seen thus far, the very encouraging data for Tippy as a monotherapy. Okay.

Certainly before the end of the year and I think that you know.

That's going to build on the clinical data that we've already seen thus far the very encouraging data for TP as a monotherapy.

Got it perfect. Thanks offered for the answers.

Troy Edward Wilson: Got it. Perfect. Thanks a lot for the answers.

Sure.

And next we'll go to Peter Lawson with Barclays.

Peter Richard Lawson: And next, we'll go to Peter Lawson with Barclay.

Hey, Thanks for taking my questions.

Peter Richard Lawson: Thank you for taking my questions. As we think about the kind of enrollment and the recommended phase two dose, just how should we think about when that data comes out and how much data we should expect to see next year, Troy?

I guess as we think about kind of enrollment and recommended phase two dose.

How should we think about when that data comes out and how much data we should expect to see next year.

Yeah. So so it's a good question Peter so as far as the phase one b is concerned as we've indicated.

Troy Edward Wilson: Yeah, so it's a good question, Peter. So as far as Phase 1B is concerned, as we've indicated, the goal is to, in fact, the requirement is to enroll at least 12 evaluable patients in each cohort and then to be able to compare those two cohorts to one another. So from Phase 1B, you'll have at least 24 valuable patients. Now, some of those may be very early on because they'll be relatively, you know, later in enrollment.

The goal is to in fact, the requirement is to enroll 12 at least 12 evaluable patients in each cohort.

And then to be able to compare those two cohorts to one another so from the phase one b you'll have at least 24 evaluable patients now some of those may be very early on because there'll be relatively you know later in enrollment.

But I think that's a good meaningful update as far as the phase one b is concerned and those patients. Unlike the one a those patients will all be either K M. T. Two E. R. N P M. One.

Troy Edward Wilson: But I think that's a good, meaningful update as far as phase 1B is concerned. And those patients, unlike in 1A, will all be either KMT2A or NPM 1. In terms of where those patients are, you know, our expectation is for, you know, to present that data at a medical meeting probably mid-year. So, you'll have some maturity, you know, of anywhere from, you know, three to six months to longer, depending on when they've come on the study, just to kind of help calibrate the quantum of data from the 1B and the timing.

In terms of where those patients are.

Our expectation is is for you know to present that data at a medical meeting probably mid year.

So you'll have some maturity of anywhere from three to six months due to longer depending on when they would come on the study just to kind of help calibrate the quantum of data from the one b and the and the timing and as from everything we can tell Peter.

Troy Edward Wilson: And from everything we can tell, Peter, enrollment is tracking to what we would have expected, and we're on a good course. So I think we're feeling good about, you know, delivering on those milestones next quarter.

Enrollment is tracking to what we would've expected and we're on a we're on a good course.

So I think we're feeling good about delivering on those milestones it next quarter.

Thank you and then just when you hit the recommended phase II dose.

Peter Richard Lawson: And then just when you hit the recommended phase two dose, what the plan is, the broader that development, you start thinking and start running combination trials. Just your process there is that partnership, or you just start running them yourselves, or is it IST's what's the plan?

What the plan is to broaden that developments you start thinking and start running combination drugs just.

Youll process, there is that partnerships or you just start running them yourselves or is it <unk>.

What's the plan.

Yes, so that's a good question and that that probably you know that could be a much longer discussion, we definitely see an opportunity in frontline.

Troy Edward Wilson: Yeah, so that's a good question and probably, you know, that could be a much longer discussion. We definitely see an opportunity in Frontline.

We also see an opportunity in in.

Troy Edward Wilson: We also see an opportunity in, in... in the earlier relapse setting. And as you know, there are several standards of care depending on the genetic makeup of the patients. We'd like to, Peter, once again say that the recommended phase two dose supports it; we'd like to go as aggressively as we can into both of those populations. In terms of strategically and tactically how you do that, it's important to us that we maintain control of the design of the trial, that we maintain control of operational execution of certain of the trials.

In the earlier a relapse setting.

And as you're aware there are <unk>.

Several standards of care, depending on the genetic makeup of the patients we'd like to Peter provided again that the recommended phase two dose supports it we'd like to go as aggressively as we can into both of those populations.

In terms of strategically and tactically how you do that it is important to us that we maintain control of the design of the trial that we may maintain control of of operational execution of certain of the trials.

That's part of what what we've been working on behind the scenes.

Troy Edward Wilson: That's part of what, you know, what we've been working on behind the scenes. There will be opportunities for ISTs, but everything is predicated on getting a recommended phase two dose. So we're doing the work, both the, you know, the preparatory work and the preclinical work to support the combinations, and we will move with the absolute greatest urgency we can into those combinations as soon as we have a recommended phase two dose that will support the, you know, the submissions to begin the phase one combination study.

There will be clearly opportunities for ice teas, but everything is predicated on getting a recommended phase II dose. So we're doing the work both the the the preparatory work in the preclinical work to support the combinations and we will move with the you know the absolute greatest urgency we can into those combinations.

As soon as we have a recommended phase two dose that will support the the submissions to begin the <unk>.

To begin the phase one combination studies.

Great. Okay. Thanks, so much.

Troy Edward Wilson: Great. Okay. Thanks so much. Pleasure. And next, we'll go to Ren Ben.

Pleasure.

And next we'll go to Ren Benjamin with JMP Securities.

Reni John Benjamin: Hey, good afternoon, guys. Thanks for taking the questions.

Hey, good afternoon, guys. Thanks for taking the questions.

I guess Troy just starting off when we think about.

Reni John Benjamin: I guess Troy is just starting off when we think

Reni John Benjamin: KO539, you know, at what point do you have any sort of metrics that you might be able to throw away in terms of a go-no-go decision or any sort of hurdles that internally you want to, you know, meet before you, you know, make the commitment to a registrational study and a path?

0539.

You know at what point.

Do you have any sort of metrics that you might be able to throw away in terms of a go no go decision or any sort of hurdles that internally.

You want to to to meet before you.

Reni John Benjamin: and a path forward.

Troy Edward Wilson: Yeah, Red, thanks for the question. So we do have a go-no-go criteria. I don't think we've articulated what they are, but they will certainly be sufficient. These are obviously 12 patient cohorts, so you're not going to get statistical power. But you would want to see a level of CRCRH that's enough to give you confidence that a properly powered trial would hit its endpoint of 20 to 30 percent, you know, CRCRH. And so that's the way to think about those go-no-go decisions. And I don't think that's of any great surprise to anyone. And then when we're thinking about, you know, the broader developmental strategy,

Troy Edward Wilson: not only as a monothea,

Troy Edward Wilson: take us through that. I mean, it seems like Venetoclax is a natural. What other sort of combinations are you thinking about? Yeah, thanks for that, Ren.

Troy Edward Wilson: And, you know, one of the ways in which 539 we think is differentiated from the competition is, you know, we're expecting and hoping it should have equivalent superior efficacy and a better safety and tolerability profile, particularly in our ability to combine it. And when I made the comment earlier in the call about, you know, the safety and tolerability are consistent, I just want to emphasize, you know, we've seen, it is a very, very well-tolerated compound. There was one incidence of pancreatitis back in the 1A. We've seen no additional evidence of that.

One of the ways in which 539, we think as differentiated from the competition is we're expecting and hoping it should have equivalent to superior efficacy and a and a better safety and tolerability profile, particularly in our ability to combine and when I made the comment earlier in the car.

Call about the safety and Tolerability is consistent I just want to emphasize.

We've seen we've seen it is a very very well tolerated compound there was one incidents back in the one a of pancreatitis. We've seen no evidence no additional evidence of that really you know no toxicities at all that we think would limit the ability either to develop the drug or to combine it.

Troy Edward Wilson: Really, you know, no toxicities at all that we think would limit the ability either to develop the drug or to combine it. But when you think about combinations, you know, the combinations depend on the genetic subtypes. So in the front line, you principally have Venetoclachs and Asocytidine in patients who are unfit, you have 7 plus 3 in the patients who are fit, and then you have to figure out how you work with the flit-3 inhibitors because there are different algorithms depending on which patient population you're in. As you move to the patient populations that are earlier relapse, then you look at, you know, you look at You may see things like Flag Ida.

When you think about combinations.

The combinations depend on the genetic subtypes. So in the frontline you principally have venetoclax and he's decided in in the patients who are unfit you have seven plus three and the patients who are fit and then you have to figure out how you work with the flip three inhibitors because.

Troy Edward Wilson: You may see, again, Flit-3 combinations. And we're doing a lot of work, Ren, to figure out how you can cover as much ground as possible with these different genetic subtypes but also move as efficiently as possible to get to the market. You, you know, you, ideally, you're setting up trials where you're able to take as many patients as possible and then they just get slotted into sort of different arms or different, you know, different combinations.

Troy Edward Wilson: All of that work is going on. Obviously, we're keeping a lot of that close to the vest because this is a super competitive field and, you know, everybody, I think, recognizes the value of moving both clinically and commercially to those earlier lines of therapy. And, you know, I think it's highly likely that there will be opportunities for registration as monotherapies, but if you want to do the best for patients and you want to drive the greatest value, you need to move with as much urgency as possible into combinations. And we're doing a lot of work behind the scenes to do just that. So I hope that gives you a little bit more color.

Reni John Benjamin: Yep, that's definitely great. And one last thing.

Reni John Benjamin: question for me regarding the phase two study of Tippy in AITL, that 32.8 months median overall survival looks really impressive to me. And I was wondering if you could either, you know, just maybe put that in context for me as well as whether these final results potentially cause you to

Reni John Benjamin: the program or potentially partner with the program, you know, going forward.

Troy Edward Wilson: Yeah, great question, and thank you for that. So, like you, we were very impressed by both the response rate in AITL and the overall survival. And there's a lot more work to be done. I mean, we're looking forward to it.

Troy Edward Wilson: You know, Dr. Wittsick is the PI. Dr. Wittzig and Dr. Foss, who's at Yale, are really, you know, two of the thought leaders. They're both super excited about this data.

Troy Edward Wilson: The interesting thing about it, Wren, is because of the high level of activity in A. AITL, there isn't a requirement for a companion diagnostic. So we're doing some work internally. We need to meet with the KOLs.

We need to meet with the Kols and obviously, we need to get some regulatory guidance and that's something that we're planning on doing to understand what are the next steps for the program but.

Troy Edward Wilson: And obviously, we need to get some regulatory guidance, and that's something that we're planning on doing to understand what the next steps for the program are. But, you know, AITL is an ultra-orphin indication, while PTCL is a little bit larger. But this is really meaningful activity, and we want to make sure we do our due diligence to understand what that opportunity versus what we're doing in head and neck, what we're doing in AML, what you're hearing, and what we're going to be doing with the next-gen FTI as far as, you know, large, solid tumor indications.

L as in ultra orphan indication P. T C L a little bit larger.

But but this is really meaningful activity and we want to make sure. We do our due diligence to understand what what's that opportunity versus what we're doing and had neck. What we're doing in AML, what you're hearing we're going to be doing with the next Gen. F. T I as far as large solid tumor indications we view this as a high class problem and I.

Troy Edward Wilson: We view this as a high-class problem, and I think we'll be able in the next, you know, months to come back to you with more color on what, if any, are the next steps for this program, for the T-cell lymphoma program with TIPI Farnip. Perfect. Thanks to Dave.

We'll be able in the next <unk>.

Months to come back to you with more color on on what if any are the next steps for this program for the for the for the T cell lymphoma program at two P font it.

Perfect. Thanks for taking my questions guys.

Troy Edward Wilson: Perfect. Thanks for taking the questions, guys.

Sure.

And next we'll go to Joe Pumpkin us with H sailing right.

Joe Penn Guinness: And next, we'll go to Joe Penn Guinness with H.C. Wainwright.

Hey, guys. Good afternoon. Thanks for taking the question most of my questions have been answered, but I wanted to focus on.

Joe Penn Guinness: Hey, guys, good afternoon. Thanks for taking the question.

Joe Penn Guinness: Most of my questions have been answered, but I wanted to focus on

Corporate question. So you guys are obviously very busy.

Joe Penn Guinness: corporate question. So you guys are obviously very busy with the current

Current studies you are about to start additional stuff. Please as well so lot going on here and I'll pose. The question. This way have you had to anticipate or adapt in any way due to the global supply chain issues that the world is I'm looking at right now.

Joe Penn Guinness: You're about to start, you know, additional studies as well. So there is a lot going on here, and I'll pose the question this way. Have you had to anticipate?

Joe Penn Guinness: or adapt in any way due to the global supply chain issues that the world is looking at right now for, you know, any of your...

For any of your activities.

Troy Edward Wilson: Yeah, Joe, that's a good question. The short answer is no.

Yeah. So that's a good question.

The the short answer is no I mean, we well the short answer is we haven't been impacted.

Troy Edward Wilson: I mean, we, well, the short answer is we haven't been impacted. The longer answer is, you know, we have a very strong cross-functional team that looks at, you know, clinical operations, clinical supply, and site activation. You know, there are still challenges in the system. Some sites are unable to take on new studies because they're still kind of digesting the fallout from the pandemic. but we really haven't seen much of an impact now in terms of the comment study, the current study.

The longer answer is you know we have a very strong cross functional team that looks at clinical operations clinical supply.

Site activation.

There are still challenges in the system some sites.

Are unable to take on new studies, because they're still kind of digesting the you know.

The the fallout from the pandemic, but we really haven't seen much of an impact now in terms of the comments study. The current study it appears that as far as as supply chain and and just clinical development activities generally that were.

Troy Edward Wilson: It appears that as far as supply chain and just, you know, clinical development activities generally go, we're, you know, I don't know if we're an outlier, but we're fortunate that we have small molecule orally available drugs that can be given on an outpatient basis. So that actually works to our advantage. But I think at this point, you know, there's relatively little, if any, impact from either the pandemic or the supply chain challenges around. It's great to hear.

I don't know if we're an outlier. We're we're fortunate that we have small molecule orally available drugs that can be given on an outpatient basis.

That actually works to our advantage, but but I think at this point you know there's relatively little if any impact from either the pandemic, where the supply chain challenges around it.

Eva Xia Privitera: Great to hear. Thanks, Troy. Pleasure. And moving on, we'll go to Eva Privatara with Callan.

Eva Xia Privitera: And moving on, we'll go to Eva Privatara with Call. Hi, thank you for taking my questions. Luckily, many of them have already been addressed. So, just a quick one. How is duration of response counted in your trials? Are patients censored when they go on to receive a transplant? Yeah, Eva, thanks for the question. Let me actually invite Dr. Stephen Dale, who's on the phone here with me, to answer your question about how duration of response is measured, particularly with respect to transplantation.

Troy Edward Wilson: Stephen, do you want to take Ava's question? Yeah, sure, thank you, Troy. Hi Eva, thanks for the question.

Stephen Dale: Yeah, sure, thank you, Troy. Hi, Eva, thanks for the question.

Stephen Dale: Yeah, so in very simple terms, you know, patients go on to transplant, so a patient who responds tracking duration of response up until the point of transplant, the data are then censored. They're always centered at that point because if they're not, then the data become confounded because you can't distinguish between transplant and the active agent. So the answer is yes, data are centered at that point.

Stephen Dale: And now I'd like to turn the call back to Troy Wilson for any additional or closing remarks. Great, thank you, Paula, and thank you all again for joining our call. We'll be participating in the Credit Suisse virtual health care conference next week.

Troy Edward Wilson: I look forward to speaking with many of you then. In the meantime, if you have any additional questions, please feel free to contact Pete, Mark, or myself. Thanks again, and have a good evening, everyone. Thank you, and that does conclude today's call. We'd like to thank everyone. You may now disconnect.

Thank you everyone for your participation you may now disconnect.