Q1 2022 Kymera Therapeutics Inc Earnings Call

Welcome to myriad Therapeutics quarterly conference call, leading the call from management are Nello me no.

Operator: Welcome to Kymera Therapeutics Quarterly Conference. Leading the call from management are Nello Mainolfi, founder and... Jared Gollob, Chief Medical Officer, and Bruce Jacobs, Chief Sunner. After Manage, We will open the call, to ask a question. Star 1 on your, Before we get started, I would like to remind everyone that some of the comments that management may make on this call include... S. Alderman in... Actual events and results could differ materially from those expressed or implied by each individual. Authorized by the U.S. Department of State.

Operator: Uncertainties and other factors including those set forth in Kymera's most recent filings with the, And any other future filings that the company may make with Dr. Koshin, No, Amy Ondurilan. Kymera disclaims any obligation to update such, I will mail him. Over to Nello Mainolfi, founder and.

<unk> founder and CEO , Jared Gala, Chief Medical Officer, and Bruce Jacobs, Chief Financial Officer.

After managements prepared remarks, we will open the call to your questions to ask a question. Please press star one on your telephone.

Before we get started I would like to remind everyone that some of the comments that management may make on this call include forward looking statements as outlined in the press release actual events and results could differ materially from those expressed or implied by any forward looking statements as a result of various risk uncertainties.

And other factors, including those set forth Inca mirrors, most recent filings with the FCC.

And any other future filings that the company may make with the S E C.

You are cautioned not to place any undue reliance on these forward looking statements and can mirror disclaims any obligation to update such statements.

I will now hand, the call over to Nello me no fee founder and CEO .

So thank you operator, and thanks, everybody for joining us on our first quarterly results conference call.

Nello Mainolfi: So thank you, operator. And thanks, everybody, for joining us in our first quarterly results conference call. We look forward to using this forum every quarter to update all our stakeholders on the progress we're making in building Kymera into a best-in-class, fully-integrated, degraded medicine company. Before we transition into the program updates, I just wanted to take a moment to reflect on some of Kymera's achievements since we founded the company, just over five years ago, and also as we near almost our two-year anniversary since our 2020 IPO.

We look forward to using this forum every quarter to update all of our stakeholders on the progress we're making in building <unk> into a best in class fully integrated.

The greater Medicine company before we transition into the program updates I just wanted to take a moment to reflect on some of cameras achievement since we founded the company.

Just over five years ago.

And also as we near almost a two year anniversary since our 2020 IPO when <unk>.

Nello Mainolfi: When CapMero was founded in 2016, we had both ambitions for the company we wanted to build. As you'll likely know by now, the foundation of the company was predicated really on leveraging what at the time was an emerging area of science, targeted protein degradation. While we weren't then, and certainly are not now, the only company engaged in TPD, I think it's fair to say that we have approached it in a very unique way, and as a result, we believe there are several important points of differentiation with respect to our strategy and our approach that still holds true today.

<unk> was founded in 2016, we have bold ambitions for the company. We wanted to build as you likely know by now the foundation of the company was predicated really on leveraging what at the time was an emerging area of signs targeted protein degradation.

While we were in Dan and typically are not now the only company engaged in PPD.

It's fair to say that we've approached in a very unique way and as a result, we believe there are several important points of differentiation with respect to our strategy and our approach. This still holds true today from a target selection standpoint, we've been guided by strict criteria, which we believe has led us to focus on unique high value targets, where there.

Nello Mainolfi: From a target selection standpoint, we've been guided by strict criteria, which we believe has led us to focus on unique high-value targets where there is a clear advantage to using a degrader versus small-molecule inhibitor or another technology, several of which you know well and we will discuss today. We remain acutely focused on those targets that address high-MET needs, have biology that has been well-validated, and where possible, can be addressed with a precision medicine approach.

It is a clear advantage to using get degree there versus small molecule inhibitor or another technology several of which you know well and we will discuss today.

We remain.

Totally focused on those targets that address high unmet need.

<unk> that has been well validated and where possible can be addressed with precision.

Precision medicine approach. We also embarked on this mission with the belief that to truly harness the full potential of TPB, we needed to invest thoughtfully, but aggressively building our read three legacy knowledge capabilities and ultimately our industry, leading <unk> toolbox, we believe our efforts here represent.

Nello Mainolfi: We also embarked on this mission with the belief that to truly harness the full potential of TPD, we needed to invest thoughtfully but aggressively in building our E3LiGaS knowledge capabilities and ultimately our industry-leading E3LiGaS toolbox. We believe our efforts here represent an important competitive advantage that we can and will leverage.

An important competitive advantage that we can and will leverage.

Nello Mainolfi: While we're building a strong pipeline of oncology-focused degraders, which happens to be the focus also of most of our peers. We believe that there is a great potential in inflammatory conditions, as evidenced by the RxR program. But we've not stopped there, as we've engaged with partners to help us target other disease areas. And in doing so, we're building a truly disease-agnostic PPD company. We have also recently unveiled our ongoing investment in targeting high-value undrug and non-ligandible proteins using small-molecule molecular glues.

While we are building a strong pipeline of oncology focused degraders, which happens to be the focus also most of our peers.

We believe that there is a great potential in inflammatory conditions as evidenced by the Eric fluid program.

But we'll not stop there.

As we've engaged with partners, who help us target other disease areas and in doing so we're building a truly disease agnostic PPD company. We have also recently unveiled our ongoing investment in targeting high volume Android and non began to both proteins using small molecule molecular glues I think it is fair to conclude that.

Nello Mainolfi: I think it is fair to conclude that both our pipeline and diverse platform investments position Chimera in a very unique place in the landscape of highly innovative biotech companies. Looking now at the present, from the ambition beginning, we have succeeded in building a company in which the targets that were on top of our list in early 16 and 17 remain our lead programs today. We have entered the clinic with three programs, each of which exemplifies meaningful first in PPD.

With our pipeline and diverse platform investments position camera in a very unique place in the landscape of highly innovative biotech companies.

Looking now at the present.

That ambition beginning we have succeeded in building a company in which the targets that we're on top of our late teen early 16, and 17 remain our lead programs. Today, we have entered the clinic with three programs each of which is simplified meaningful first in PPD.

Nello Mainolfi: With our ARAC4 degrader, KT474, which is the first hetero-bifunctional degrader for immune inflammatory indications, we launched the first randomized placebo-controlled trial in healthy volunteers in the TPD industry. With KT333, our STAT3 degrader, we're the first company to bring a hetero-bifunctional degrader against an undrug transcription factor into the clinic. And KT413, our dual degrader of IRAG4 and imid substrates, has the potential to be the first therapy in diffuse large B-cell lymphoma targeting a genetically defined subset of patients.

We are in Iraq for the greater T. T 40, <unk> four which is the first headroom by functional degree there for immune inflammatory indications, we launched the first randomized placebo controlled trial in healthy volunteers.

The TPB industry with K T 3333 degree there were the first company to bring in headroom by functional degrader against <unk> transcription factor into the cleaning.

And Keith <unk>, our dual degree there of Iraq before it even substrates has the potential to be the first therapy in diffuse large b cell lymphoma targeting a genetically defined subset of patients and last but certainly not least we are excited to continue to progress our MDM to degree they are a key tier two.

Nello Mainolfi: And last, but certainly not least, we are excited to continue to progress our MDM2 degrader, KT253, forward to IND submission later this year. While we have not disclosed much about all the work we're doing in our discovery pipeline, I hope you all appreciate that the four disclosed pipeline programs represent only a fraction of what we hope to deliver from the significant investments we've made in our platform and pipeline over the years.

Five three forward to IMD submission later this year.

While we have not disclosed much about all the work we're doing in our discovery pipeline I Hope you all I appreciate that the four disclosed pipeline programs represent only a fraction of what we hope to build either from the significant investments we've made in our platform and pipeline over the years as we highlighted in the press release this morning.

Nello Mainolfi: As we highlighted in the press release this morning, 2022 is setting up to be a year rich in data, milestones, and scientific progress at Kymera. Jared will walk you through our recent progress and our goals of 2022 for each of our disclosed programs. Before turning the call to Bruce for a financial update, I will then finish with some concluding remarks before handing the call to the operator to facilitate a Q&A session in which Jared, Bruce, and myself will be available. Jared?

In 2022 was setting up to be a year setting up to be a year reach in data milestones in St. Pubic progress at Chimera, Jared who will walk you through our recent progress and our goals of 2022 for each of our disclosed programs.

Before turning the call to Bruce for a financial update I will then finish with some concluding remarks before handing the call to the operator to facilitate the Q&A session with Jared Bruce and myself will be available Jared.

Jared Gollob: Thanks, Nello. Starting with our oncology programs, we are pleased to report that the three disclosed oncology programs, STAT3, Arachamid, and MDM2, are all tracking as expected. First, I will discuss our STAT III program. KT333, as mentioned, is our lead stat-free degrader. As a brief background, STAT3 is a transcriptional regulator that has been linked to numerous cancers and other inflammatory and autoimmune diseases, and it is a target that has long been considered undruggable. Our focus here is on developing selective SFAT3 degraders for the treatment of hematological malignancies and solid tumors, as well as autoimmune and fibrotic diseases.

Hello.

Starting with our oncology programs. We are pleased to report that the three disclosed oncology program stat, three IRAK <unk> and <unk> are all tracking as expected.

First I will discuss our stat three program.

<unk> hundred 33 as mentioned is our lead stat three integrator.

Backgrounds that three is a transcriptional regulator that has been linked to numerous cancers and other inflammatory and autoimmune diseases and it is a target that has long been considered undruggable.

Our focus here is on developing selective stat, three integrators for the treatment of Hematological malignancies, and solid tumors as well as autoimmune anti fibrotic diseases.

Jared Gollob: We believe our STAT3 degraders have the potential to provide a transformative solution to address multiple STAT3-dependent pathologies. In terms of a clinical update, recall that we received IND clearance from FDA in 4Q21. The first clinical site was activated in 1Q22, and the trial is actively recruiting patients. As a reminder, KTEA-333 is being evaluated in adult patients with relapsed, refractory, liquid, and solid tumors, including aggressive lymphoma. Dose escalation is expected to proceed throughout 2022, and we look forward to presenting the first patient data, including preliminary safety and proof-of-mechanism clinical data, in the second half of 2022. Moving now to Arachamid, KT413 is a novel hetero-bifunctional degrader that targets degradation of both IRAK4 and the imid substrates icarose and ilose with a single small molecule.

We believe our SaaS or integrators have the potential to provide a transformative solution to address multiple statutory dependant pathologies.

In terms of a clinical update recall that we received IND clearance from FDA in <unk> 'twenty one.

The first clinical site was activated in <unk> 22, and the trial is actively recruiting patients.

As a reminder, <unk> three is being evaluated in adult patients with relapsed refractory liquid and solid tumors, including aggressive lymphomas.

Dose escalation is expected to proceed throughout 2022, and we look forward to presenting the first patient data, including preliminary safety and proof of mechanism clinical data in the second half of 2022.

Moving now to Iraq committed Caky 413 is a novel hetero by functional the greater that targets degradation in both Iraq for and the image substrates, <unk> and <unk> with a single small molecule.

Jared Gollob: KT413 was designed to address both the IL-1R TLR and the type 1 interferon pathway synergistically to broaden activity against MITEI-88 mutant B-cell malignancies. KT413 is on a similar timeline as STAT3, having received IND clearance from FDA late last year. The first clinical site was activated in 1Q22 and patient recruitment is underway. As a reminder, the Phase I trial for KT413 is focused on adult patients with relapsed, refractory B-cell lymphomas, including mighty 88-Newton diffuse large B-cell lymphoma, or DLBCL.

Katy for one three was designed to address both the <unk> and the type one interferon pathway synergistically to broaden activity against <unk> 88, B cell malignancies.

80, 413 is on a similar timeline as stat, three having received IND clearance from FDA late last year.

First clinical site was activated in <unk> 'twenty, two and patient recruitment is underway.

As a reminder, the phase one trial for <unk> three is focused on adult patients with relapsed refractory b cell lymphomas, including <unk> 88, mutant diffuse large b cell lymphoma or <unk>.

Jared Gollob: Our plans remain to present KT413's first patient data, including preliminary safety and proof of mechanism clinical data in the second half of 2022. Before concluding with an update on our IRAC4 program, I wanted to touch briefly on MDM2, a program we announced for the first time at our R&D day late last year. As we have shared, we are very excited about the potential of this program. MDM-2 is the crucial regulator of the most common tumor suppressor, P53, which remains intact or wild-type in more than 50% of cancers.

Our plans remain to present KD four when three its first patient data, including preliminary safety and proof of mechanism clinical data in the second half of 2022.

Yeah.

Before concluding with an update on our Iraq for program I wanted to touch briefly on MDM to a program we announced for the first time at our R&D day late last year as.

As we have shared we are very excited about the potential of this program.

MTM too is the crucial regulator of the most common tumor suppressor P 53, which remains intact or wild type and more than 50% of cancers.

Jared Gollob: Based on preclinical data, we believe our highly potent MDM2 degrader, KT253, has the ability, unlike small molecule inhibitors, to suppress the MDM2 feedback loop and thus the potential to rapidly induce apoptosis even with brief exposures. We believe KT253 has the potential to be effective in a wide range of hematological malignancies and solid tumors with functioning T53. Just a few weeks ago, we shared preclinical data at AACR highlighting the biological superiority of MDM-2 degradation over inhibition.

Based on preclinical data, we believe our highly potent MDM to the greater K T to five three as the ability. Unlike small molecule inhibitors to suppress the MDM to feedback loop and best potential to rapidly induce apoptotic this even with brief exposures.

We believe <unk> has the potential to be effective in a wide range of hematological malignancies, and solid tumors with functioning <unk> 53.

Just a few weeks ago, we shared preclinical data at ACR, highlighting the biological superiority of MGMT degradation over inhibition, specifically, we presented preclinical data for <unk> three that demonstrated extremely potent in vitro cell, killing and in vivo anti tumor activity with intermittent dosing that is <unk>.

Jared Gollob: Specifically, we presented preclinical data for KT253 that demonstrated extremely potent in vitro cell killing and in vivo anti-tumor activity with intermittent dosing that is superior to data reported for existing small molecule inhibitors and indicates the potential for improved efficacy and safety with degradation versus inhibition. You can find that poster along with all other publications in the scientific resources section of our website.

<unk> the data reported for existing small molecule inhibitors and indicates the potential for improved efficacy and safety with degradation versus inhibition.

You can find that poster along with all other publications in the scientific resources section of our website.

As planned Katie five three to five three is currently in IND, enabling activities to support an <unk> filing in the second half of 2022.

Jared Gollob: As planned, KT253 is currently in IND-enabling activities to support an IND filing in the second half of 2022. Finally, I will cover our IRAC4 program and our lead candidate, KT474. As previously disclosed, late last year we completed dose escalation in the single ascending dose and multiple ascending dose portions of our Phase I clinical trial, where we enrolled over 100 healthy adult volunteers. As reported, initial data demonstrated near-complete IRAC4 knockdown in PBMC and skin as well as robust ex vivo inhibition of multiple disease-relevant cytokines with a favorable safety profile.

Finally, I will cover our Iraq for a program and our lead candidate <unk> 474.

Jared Gollob: Specifically, in the multiple ascending dose portion of the trial, where subjects received 14 daily doses and we explored a range of doses from 25 to 200 milligrams, robust IRAC4 degradation was seen across all dose levels, with up to 98% reduction in PBMC at steady state between day 7 and 14, plateauing after 100 milligrams. In skin, IRAC4 levels were also reduced to near the lower limit of detection by day 14 at the top dose, but had not yet reached steady state, suggesting that continued dosing beyond 14 days would likely result in further declines in IRAC4 levels at daily doses of 50 to 200 milligrams. Finally, ex vivo cytokine induction by TLR agonists showed greater than 50% inhibition of most cytokines and maximum inhibition of 85% in the 100 mg dose group.

As previously disclosed late last year, we completed dose escalation in the single ascending dose and multiple ascending dose portions of our phase one clinical trial, where we enrolled over 100 healthy adult volunteers.

As reported initial data demonstrated near complete Iraq Board knockdown in <unk> and skin as well as robust ex vivo inhibition of multiple disease relevant cytokines with a favorable safety profile.

Specifically in the multiple ascending dose portion of the trial, where subjects received 14 daily doses and we explored a range of doses from 25 to 200 milligrams robust Iraq poor degradation was seen across all dose levels with up to 98% reduction in PBC at steady state between day, seven and 14.

Going after 100 milligrams.

In skin Iraq War levels were also reduced to near the lower limit of detection by day, 14th at the top dose, but had not yet reached steady state, suggesting that continued dosing beyond 14 days would likely result in further declines in Iraq for leveled at daily doses of 50 to 200 milligrams.

Finally, ex vivo cytokine induction by <unk> agonist showed greater than 50% inhibition of most cytokines and maximum inhibition of 85% and the 100 milligram dose group.

This robust inhibition was seen in conjunction with greater than 90%, Iraq, <unk> knockdown and monocytes.

That previously disclosed data as context, I will now comment on our plans for 2022, including a few recent developments.

Jared Gollob: This robust inhibition was seen in conjunction with greater than 90% IRAC4 knockdown in monocytes. That previously disclosed data as context, I will now comment on our plans for 2022, including a few recent developments. We have selected the dose equivalent of 100 mg in the fed state to take into Part C, the patient portion of the Phase I trial. Based on our clinical experience to date, we believe that the 100 mg dose is the level at which we have maximized the pharmacology of KT474 and which will drive robust IRAC4 degradation leading to TLR-IO1R pathway inhibition in multiple different disease-relevant cell types that can impact inflammation and result in disease-modifying clinical activity.

We have selected the dose equivalent of 100 milligrams in the fed state to take into part C. The patient portion of the phase one trial.

Based on our clinical experience to date, we believe that the 100 milligram dose at the level at which we have maximized the pharmacology K T 474, and which will drive robust Iraq for degradation, leading to teal or <unk> pathway inhibition in multiple different disease relevant cell types that can impact inflammation and result in <unk>.

These modifying clinical activity.

Jared Gollob: Having observed in SAD an increase in exposure with KT474 in the FET state versus FASFID, we are enrolling an additional SAD cohort to determine the 100 mg dose equivalent in the FET state. Once we have those results, we will then proceed to the patient cohort portion of the trial. With respect to the patient cohort, we have made a modification to the study design. Specifically, we will be extending the dosing duration from 14 to 28 days.

Having observed in <unk> and an increase in exposure with <unk> said before in the fed state versus fasted, we are enrolling an additional cohort to determine the 100 milligram dose equivalent in the fed state.

Once we have those results. We will then proceed to the patient cohort portion of the trial.

With respect to the patient cohort, we have made a modification to the study design.

Specifically, we will be extending the dosing duration from 14 to 28 days.

Jared Gollob: This decision was made in conjunction with our partner, Sanofi, and we recently aligned with FDA on this protocol modification. Many of you have asked about our ability to track clinical endpoints in this portion of the trial, which we had not planned to do with just 14 days of dosing. But with this change to 28 days of dosing and 14 days of follow-up, we have now added several exploratory clinical endpoints, including the eczema area and severity index, or EASI, for atopic dermatitis, total abscess and inflammatory nodule count for hydradenitis separativa, as well as additional measures of symptoms and physician or investigator global assessments for both diseases.

This decision was made in conjunction with our partner Sanofi and we recently aligned with FDA on this protocol modification.

Many of you have asked about our ability to track clinical endpoints in this portion of the trial, which.

Which we had not planned to do with just 14 days of dosing.

Ah witness change to 28 days of dosing in 14 days of follow up we have now added several exploratory clinical endpoints, including the eczema area and severity index or E. ASI for atopic dermatitis, total abscess and inflammatory nodule count for Hidradenitis Suppurativa.

As well as additional measures of symptoms and physician or investigator global assessment for both diseases.

We plan to share the results of the patient cohort in the second half of this year as previously guided.

Jared Gollob: We plan to share the results of the patient cohort in the second half of this year as previously guided. Finally, prior to selecting the dose for the patient cohort, we undertook a comprehensive analysis of all safety data from the SAD and MAD portions of Phase I, which recently included unblinded results. Consistent with what we have previously disclosed, the unblinded safety analysis showed KT474 to be safe and well tolerated with no serious adverse events and no treatment discontinuations.

Finally prior to selecting the dose for the patient cohort, we undertook a comprehensive analysis of all safety data from the Sandy and MH portions of Phase one, which recently included unblinded results.

Consistent with what we have previously disclosed the unblinded safety analysis showed 84, seven and four to be safe and well tolerated with no serious adverse events and no treatment discontinuation.

A full analysis of 24 hour holter ecg's as well as safety Ecg's that were part of the Phase One study did not show any arrhythmias or other ECG adverse events.

Jared Gollob: A full analysis of 24-hour Holter ECGs, as well as safety ECGs that were part of the Phase I study, did not show any arrhythmias or other ECG adverse events. We did identify a modest, non-adverse, non-dose dependent, 10 to 20 millisecond prolongation of QTC relative to baseline only after multidosing in the MAD portion of the trial. This modest effect plateaued by day 7 and completely reversed after day 14 following the completion of dosing. Importantly, the QTC interval itself remained less than 450 milliseconds, and therefore the QTC prolongation did not qualify as a grade one adverse event.

We did identify a modest non adverse non dose dependent 10 to 20 milliseconds prolongation of Q T C relative to baseline only after multi dosing in the <unk> portion of the trial.

This modest effect plateaued by day, seven and completely reversed after day 14, following the completion of dosing.

Importantly, the Q T C interval itself remain less than 450 milliseconds and therefore, the <unk> prolongation did not qualify as a great one adverse event.

FDA was informed of the full safety data set including the comprehensive <unk> analysis and did not objected to the proposed dose selection as well as the protocol adjustments to part C. That include 28 days of dosing both to enable evaluation of exploratory clinical endpoints and to extend safety.

Jared Gollob: FDA was informed of the full safety data set, including the comprehensive QTC analysis, and did not object to the proposed dose selection, as well as the protocol adjustments to Part C that include 28 days of dosing, both to enable evaluation of exploratory clinical endpoints and to extend safety monitoring. Our broader clinical plans, aside from this adjustment to the patient cohort, remain unchanged and we are excited to advance KT474 through further clinical development. Before Nello concludes the call with some closing remarks, I will hand the call to Bruce Jacobs, our Chief Financial Officer, who will share some brief comments on our financial results for the first quarter. Bruce?

On a train.

Our broader clinical plans aside from this adjustment to the patient cohort remain unchanged and we are excited to advance <unk> 474 through further clinical development.

Before now we will conclude the call with some closing remarks, I will hand, the call to Bruce Jacobs, Our Chief Financial Officer, who will share. Some brief comments on our financial results for the first quarter. Bruce. Thanks shared I will keep my comments here brief for the quarter, we recognized $9 6 million of revenue. This total effect reflects red.

Bruce Jacobs: Thanks, Jared. I will keep my comments here brief. For the quarter, we recognize $9.6 million of revenue. This total reflects revenue recognized pursuant to our Sanofi and Vertex collaborations. At the end of the quarter, our deferred revenue total on the balance sheet was approximately $93 million. That reflects partnership revenue that we expect to recognize over the next several years. With respect to operating expenses, our need for the quarter was $35.9 million, of which about $3.9 million represented non-cash stock-based compensation.

<unk> recognized pursuant to our Santa <unk> and vertex collaborations at the end of the quarter. Our deferred revenue total on the balance sheet was approximately 93 million that reflects partnership revenue that we expect to recognize over the next several years with respect to operating expenses R&D for the quarter was $35 9 million of which about $3 nine.

Represented noncash stock based compensation, the adjusted cash R&D spend of $32 million, which again excludes the stock based compensation reflects about a 5% decrease from the comparable amount in the December quarter, our G&A spending for the quarter was $10 6 million 4 million of which was noncash stock based comp.

Bruce Jacobs: The adjusted cash R&D spend of $32 million, which again excludes the stock-based compensation, reflects about a 5% decrease from the comparable amount in the December quarter. Our G&A spending for the quarter was $10.6 million, $4 million of which was non-cash stock-based comp. The adjusted cash G&A spend of about $6.6 million, again excluding stock-based compensation, reflects a 2% decrease from the comparable amount in the December quarter.

The adjusted cash G&A spend of about $6 6 million again, excluding stock based compensation reflects a 2% decrease from the comparable amount in the December quarter, and finally for my part we exited <unk> with cash and equivalents of approximately $523 million that provides a runway based on our current anticipated spending.

Bruce Jacobs: And finally, for my part, we exited 1Q with cash and equivalents of approximately $523 million. That provides a runway based on our current anticipated spending levels into 2025. And please recall, we do not include in our cash runway any payments or milestones that we have not yet received.

Levels into 2025, and please recall, we do not include in our cash runway any payments for milestones that we have not yet received I will now turn the call back to narrow for some concluding remarks, thanks, Bruce and Jared in conclusion, I think I can.

Nello Mainolfi: I'll now turn the call back to Nelo for some concluding remarks. Thanks, Bruce and Jared. In conclusion, I think I can clearly say that we're very excited about where Chimaera is at the moment.

Clearly say that we're very excited about where it came in right at the moment, we have an exciting first in class pipeline. There is progressing through the clinic a best in class platform and discovery engine, which will continue to hear about as we disclose more programs and data productive partnerships with vertex and Sanofi that allow us to extend across.

Nello Mainolfi: We have an exciting first-in-class pipeline that is progressing through the clinic, a best-in-class platform and discovery engine of which we'll continue to hear about as we disclose more programs and data, productive partnerships with Vertex and Sanofi that allow us to extend across multiple disease areas, and as you've heard from Bruce, a very strong cash position that enables us to continue to invest in high-value programs and generate several important data sets in the next few years. In 2022, we're looking forward to generating key proof-of-mechanism data in two oncology clinical programs, KT413 and KT333, against two drug targets and pathways, Arachamid and SpA3, both with broad franchise potentials.

People disease areas and as you heard from Bruce at very strong cash position that enable us to continue to invest in high value programs and generate several important data sets in the next few years 2022, we're looking forward to generating key proof of mechanism data into oncology clinical programs <unk>.

<unk> hundred 33 against two drug targets and pathways, Iraq comedians that three.

Both with broad franchise potentials.

Nello Mainolfi: We're also very excited to add our fourth clinical program later in the year with our MDM2 degrader, KT253, which we believe will have large clinical potential. With regards to 474, as you've heard from Jared, after consultation with the FDA, we've extended our Phase I patient study to 28 days to generate even more potentially de-risking data, including the possibility of early clinical proof of concept. We strongly believe that this mechanism has the potential to be best-in-class, small-molecule anti-inflammatory drug, and excited to explore clinical activity in HSAD and eventually in a wide variety of additional indications.

We're also very excited to add our fourth clinical program later in the year with our MDM to degree the acuity <unk> III, which we believe will have large clinical potential with regards to 47 474 as you've heard from Jared after consultation with the FDA, we've extended our phase one patient study to 28 days.

To generate even more potentially derisking data, including the possibility of early clinical proof of concept. We strongly believe that this mechanism has the potential to be best in class small molecule antifungal drug and excited to explore clinical activity in HSA and eventually in a wide variety of <unk>.

<unk> indications.

Nello Mainolfi: I'd like to thank, first of all, the Kymera team for every day pushing boundaries in a completely new drug modality and for continuing to execute on our very ambitious goals. I would like to thank our collaborators for enabling us to operate efficiently in a globally challenging landscape, our partners for the rich contributions, and last but not least, all the healthy volunteers and patients that allow us to advance the development of our potentially transformative therapies.

I'd like to thank first of all camera team for everyday pushing boundaries in a completely new drug modality and for continuing to execute on a very ambitious goals I would like to thank our collaborators for enabling us to operate efficiently efficiently in a globally challenging landscape.

<unk> for the reach contributions and last but not least all the healthy volunteers and patients that allow us to advance the development of a potentially transformative therapies.

Nello Mainolfi: Finally, I would like to thank all of you that have taken time this morning for our first quarterly call and looking forward to a rich Q&A. I'll now hand the microphone back to the operator so that we can take your questions.

Finally, I would like to thank all of you that have taken time. This morning for our first quarterly call and looking forward to it reached Q&A I'll now hand, the microphone back to the operator, so that we can take your questions. Thank you.

Yes.

Thank you at this point, we will open the call for questions to ask a question. Please press star one on your telephone to withdraw your question press the pound or hash key.

Operator: Thank you. Thank you. At this point, we will open the call for questions, to ask a question. Star 1 on your telephone.

Operator: To withdraw the question, press the pound or, Our first question comes from Ellie Merle with UBS, please go ahead. Hey, guys, thanks for taking the question and congrats on all the progress. Maybe just first on the 28-day patient cohort, I guess, do you still anticipate enrolling 20 patients or, you know, given sort of the lengthening of the study, do you anticipate perhaps enrolling more patients as well? And then if you could just comment on the anticipated mix between atopic derm and HF patients in that cohort.

First question comes from Ellie Merle with UBS. Please go ahead.

Thanks for taking my question and congrats on the program.

Maybe just first.

Okay.

Bart I guess do you still anticipate enrolling 20.

Go ahead sorry.

Yes.

Lengthening of B W.

Perhaps enrolling more patients with Wow and then if you could just comment on the anticipated mix between atopic derm.

Jeff.

That cohort.

Operator: And then second, just on the... For elongation, can you give us just a little bit more color on what was seen sort of like the number of patients, which dose levels? And I think you said it wasn't considered grade one, even. I mean, just any more color there would be helpful.

And then second does.

The Qt prolongation can you give us just a little bit more color.

Hey, Sam.

Which dose level.

Nello Mainolfi: And I guess also when you did the unblinding of the safety data, just maybe what dose levels the mild heart palpitations were seen at. Thanks. Thanks Ellie, this is Nello here.

I think you said it was that considered save one Ivan I mean, just any more color there.

Would be helpful and I guess also what you did see.

The safety data, just maybe what dose levels.

That mild hurt competition horses.

Cool. Thanks. Thanks Ali this is nello here, so maybe I'll just give a brief overview and then I'll, let Jared here comment on the specifics so.

Nello Mainolfi: So maybe I'll just give a brief overview and then I'll let Jared here comment on the specifics. So as we said, the extension of the study to 28 days was done mostly driven by our desire to pursue an opportunity to understand even further the PD and potential clinical profile of the molecule, given the competitive space, and to be honest, given the profound pharmacology that we've observed so far. Also, after unblinding the study, we wanted to take the opportunity to extend the duration of dosing to further our understanding of the safety, which so far has been actually quite promising.

So as we said the extension of the study to 28 days was done mostly driven by that.

Our desire to pursue an opportunity to understand even further.

PD and potential clinical profile of the molecule.

Given the competitive space and to be honest given the profile pharmacology.

So far.

Also after.

Blinding the study we wanted to take the opportunity to extend the duration of dosing too.

Further our understanding of the safety, which so far has been.

Nello Mainolfi: Maybe, Jared, you can comment a bit on the unblinding and what we've learned, as well as I think Ellie's question was also about this modest finding that we have with QCC of which doses and how it was detected. Sure.

Actually quite promising.

Maybe John you can comment a bit on the blinding.

Learn as well as I think <unk> question was also about.

These are modest finding them, we have with PCC of which doses.

Hi was detected sure yes.

Jared Gollob: As we described on the call, we were always planning to unblind and really have a comprehensive look at all the safety data once we decided that we weren't going to dose escalate further and when we were going to then choose our dose to bring it to Part C. The unblinding really showed that really the adverse events that we saw with the blinded analysis still remain the primary adverse events that we saw in a relatively small proportion of patients, including headache that was predominantly mild, palpitations that were also predominantly mild and self-limited, as well as several subjects with nausea. It turned out that the adverse events, these in particular, were seen in the drug arm, not in the placebo arm, and that was not unexpected. Again, just to note that these were relatively few in number, they were self-limited, and they were predominantly mild.

We described on the call.

We're always planning to online and really have a comprehensive look at all the safety data once we decided that we weren't going to dose escalate further and when we were going to then choose our dose to bring into part C.

On blinding really showed that really the adverse events that we saw was a blinded analysis still remain the primary adverse events that we saw in a relatively small proportion of patients, including headaches that was predominantly mild competitions that were also predominantly mild and self limited as well as several subjects with <unk>.

With nausea.

It turned out that the.

These adverse events. These in particular, we're seeing in the drug arm in the placebo.

<unk> arm.

And that was not unexpected and again just to note that these were relatively few in number they were self limited and they were predominantly mild.

Jared Gollob: In terms of the QTC finding, as we described, this was not seen in the SAD portion of the study and was not seen following the first dose of the MAD. It was only seen after multidosing. This was a modest effect.

In terms of the UTC finding.

As we described this as not being in the center portion of the study and was not following the first dose of <unk> was only seen after multi dosing. This was a modest effect. This 10 to 20 milliseconds increase.

Modest effect.

Jared Gollob: This 10 to 20 millisecond increase is a modest effect. This change in QTC is well below the 60 millisecond threshold that is associated with risk of arrhythmia. Also importantly, the QTC interval itself remained less than 450, which is essentially within the normal range, which is also well below the 500 millisecond threshold, which confers risk of arrhythmia. We note this modest change in QTC, but it's important to note that this is well away from the threshold associated with any possibility of clinical adverse events, such as arrhythmia.

The change in UTC is well below the 60 mile. A second threshold that is associated with risk of arrhythmia and also importantly, the qt interval itself remain less than $4 50, which is essentially within a normal range, which is also well below the 500, rather second a threshold at which confirmed and risk of <unk>.

So we note this modest change in Q D C. But it's important to note that this is.

Well away from the threshold associated with any sort of possibility.

The possibility of sort of clinical adverse events such as arrhythmia.

Jared Gollob: Maybe I will just add one thing as we go, Bruce, if we go to the next question here. So why are we sharing a non-adverse event in this call today, as obviously never made to the table of adverse events, and actually we only learned it afterwards? And the reason that we're doing so is just because we want to keep our style of communication transparent and continue to maintain a high level of rigor and credibility. Obviously we can discuss for the next half an hour this particular finding. Hopefully we get to talk about the other things.

Okay. Thanks, So maybe I'll just add one thing as we go Bruce if we go to the next question here.

So why are we sharing and non adverse event in this call today.

Obviously never made to the table a adverse event and actually we only learned it afterwards and.

The reason that we're doing so because we want to keep.

<unk> kind of style of communication transparent and continue to maintain high level of rigor and credibility and obviously, we can discuss for the next half an hour. These particular finding but.

Hopefully, we get to talk about the other things as well.

Thank you. Your next question is from Brad <unk> with Stifel. Please go ahead.

Operator: Thank you. Your next question is from Brad Canino with Stiefel. Please go ahead.

Good morning, I appreciate the update.

Nello Mainolfi: Good morning, appreciate the updates. On the newly added clinical endpoints for KT474, you know, I've seen data with the TNFs and IL-1 agents, in HS particularly, where improvements don't max out until about eight weeks. So do you have any HS benchmarks in mind when you're thinking about the four-week time point?

The newly added clinical endpoints for Kt 474, I've seen data with the TNF and IL, one agents in Hs, particularly where improvements don't Max out until about eight weeks. So do you have any hs benchmarks in mind, when you're thinking about the four week time point, and I'm, especially asking and consideration of Pfizer.

Nello Mainolfi: And I'm especially asking in consideration of Pfizer's announcement to discontinue their iRac4 small molecule this morning. And then looking forward to the other development opportunities for 474, I'd like to ask about your takeaways from the recent Nature publication that implicated TLR7 as the central signaling pathway in lupus, and whether that might change your disease development prioritization at all. Thank you. Yeah. Thanks, Brad.

Announcement to discontinue their Iraq for small molecule this morning.

And then looking forward to the other development opportunities for $4 74, I'd like to ask about your takeaways from the recent nature publication that implicated CLR seven as the central signaling pathway in lupus and whether that might change your disease development prioritization at all thank you, yes. Thanks Brad.

Great questions. So I'll take a bit of it and then I'll, let Jerry comment on the more specific points.

Nello Mainolfi: It's always, you know, great questions. So, I'll take a bit of it and then I'll let Jared comment on the more specific point. I just would like to kind of reiterate the 28 days. So, we're not running a 28-day study to produce definite proof-of-concept data. I think, as we said, we have given our preclinical top studies. We have opportunities to extend the duration of those into 28 days to firm up PKPD as well as early sign of clinical efficacy with also the safety profile. And to really fully, maybe not fully, but to further appreciate the risk-reward profile of the molecule.

I just would like to kind of reiterate the 28 days. So we're not running a 28 day study to produce definite proof of concept data I think as we've said we have given.

Our preclinical Tox studies, we have opportunities to extend the duration of those into 28 days to firm up PK PD as well as early signs of clinical efficacy with also the safety profile and to really fully maybe not fully but to further appreciate the risk reward profile of the mall.

Thank you.

Nello Mainolfi: So, I will not comment specifically on other drugs in four weeks of study, but I think it's fair to say, both across the ADNHS, that within four weeks, you know, active drugs, you start to see some separation from placebo in well-controlled studies, and so we feel like it will be probably short-sighted of us not to measure clinical endpoints. Again, not with the expectation for us to say we have clinical proof of concept, just because I want to reiterate this would be an open-label study, but just to start to further create a strong relationship with RPD, and again, as I said, early potential clinical endpoints.

So.

I will not comment specifically on other drags in four weeks the study, but I think it's fair to say both across eight DNA Chet then within four weeks.

Active drugs do you start to see some separation from from placebo in well controlled studies.

And so we feel like it will be.

Probably short sighted robust not to measure clinical endpoints again noted the expectations for us to say, we have clinical proof of concept just because I want to reiterate this would be an open label study, but just as to start to further create strong relationships with our PD and again as I said early potential.

Clinical endpoints. So it's to further that relationship that we've been trying to build from the early days of the development of this program and.

Nello Mainolfi: So, it's to further that relationship that we've been trying to build from the early days of the development of this program. And I'll let Jared comment on where are the comps that he's keeping an eye on.

And I'll, let John comment on where are the comps that you.

Keeping an eye on I wanted to address you've made to Pfizer coins in the other indications with regards to Pfizer, yes, we've learned that today as well 20 minutes ago, you kind of an hour ago.

Nello Mainolfi: I wanted to address, you made the Pfizer point and the other indications. With regard to Pfizer, yes, we've learned today as well, 20 minutes ago, I think, half an hour ago, that maybe just, not to correct you, but to specify, I think their HS study, the HS development seems to be halted, but the IRAE trial continues to move forward. I don't want to speculate, especially not on this call.

Maybe just not to correct you, but to specify I think they're Hs study.

The IHS divestments seems to be.

Halted, but DRA trials as continue continues to move forward, we I don't want to speculate, especially not on this call.

Nello Mainolfi: Clearly, the important thing doesn't seem to be, at least based on the fact that other studies are ongoing, the safety concern, and then we really don't know the data in HS versus that, the three-armed study with the JAK inhibitor and TIK2. So I don't know whether there's been some prioritization in that pipeline, but we'll have to see. And then, you know, with regard to the breadth of opportunities, as you know, we have a slide on our deck that points to several opportunities in TH1, TH17, TH2 biology. Yes, we're well aware of TLR7 data, recent human genetics data, pointing to a really strong correlation to lupus.

Clearly, it's an important thing and doesn't seem to be at least based on the fact that other studies are ongoing safety concern and then we really don't know the data in Hs versus there. The three arm study with the JAK inhibitors or two so I don't know whether theres been some prioritization in that pipeline, but we'll efficacy.

And then with regards to the breadth of opportunities as you know we have a slide on our deck that points to.

Several opportunities in the th one th 17 th two biology, yet, we're well aware of DLR seven data recent human genetics data pointing to a really strong correlation to lupus lupus is one of those diseases that we're exploring with our partners.

Nello Mainolfi: Lupus is one of those diseases that we're exploring with our partner Sanofi in terms of priorities. And so as we continue to advance the program, we will do our best to exploit fully the potential of this mechanism. Jared, any comment on the, you know, let's say the comms?

In terms of priorities and so as we continue to advance the program, we will do our best to exploit fully the potential of this mechanism.

Any comment on.

The comps, yes, maybe just to touch on this.

Jared Gollob: Yeah, maybe just to touch on this, you know, in terms of, you know, why extending also to 28 days? I think one of the main drivers for our decision to extend to 28 days of dosing, you know, came from our review of the pharmacodynamic data where we saw that while, you know, knockdown in peripheral blood really reached steady state, you know, after seven days of dosing, in skin, you know, we had not reached steady state after 14 days of dosing.

In terms of.

Why extending also the 28 days I think one of the main drivers for our decision to extend the 28 days of dosing came from a review of the Pharmacodynamic data, where we saw that while the lockdown and peripheral blood really reached steady state after seven days of dosing and skin. We had not reached steady state after 14 days of dosing.

Jared Gollob: And so being able to extend dosing to 28 days would give us the opportunity to dose long enough to reach steady state knockdown in skin. And since in part C, what's very important to us is now obtaining skin biopsies of active inflamed skin lesions and being able to show not just knockdown of IRAC-4 in the skin, but also impact on disease-relevant inflammatory biomarkers in the skin. We thought it was important to extend to 28 days to give us the best chance of really showing that sort of pharmacology in diseased skin.

So being able to extend dosing of 28 days, but give us the opportunity.

To Joe's long enough to reach steady state knockdown in skin and since in part C. What's very important to US now obtained skin biopsies of active inflamed skin lesion and being able to show that just knockdown of Iraq for in the skin, but also impact on disease relevant inflammatory biomarkers in the skin. We thought it was important to extend the 28 days to give us the best chance I've really showing.

That's sort of pharmacology and disease again now in terms of the comps at 28 days. We know for example in the Humira pivotal studies in Hs and the two picks in pivotal studies and if you look at the curve for their various primary endpoints or even their secondary endpoint you can see that at 28 days of Delaware.

Jared Gollob: Now, in terms of the comps, you know, at 28 days, you know, we know, for example, in the Humira pivotal studies in HS and the Dupixent pivotal studies in AD, if you look at the curves, you know, for, you know, their various, you know, primary endpoints or even their secondary endpoints, you can see that at 28 days, as Nelo was saying, you can start to see separation clearly from placebo.

And you can start to see separation clearly from placebo and we think that there is a potential opportunity to protect.

Jared Gollob: We think that there is a potential opportunity to detect an initial sort of exploratory signal of clinical efficacy, and what would be nice for us is to be able to sort of connect a signal of efficacy with, you know, pharmacodynamic effect or proof of biology showing impact on IRAC-4 and inflammatory biomarkers in both the skin and the blood. So being able to make that connection in Part C, we think would, you know, really help to further de-risk. So your next question comes from Michael Schmidt with Guggenheim, please go ahead. Hey, good morning. This is Paul on for Michael.

An initial sort of exploratory signal of clinical efficacy and what would be nice for us is to be able to sort of connect a signal of efficacy with the pharmacodynamic effect of proof of biology, showing impacts on Iraq for an inflammatory biomarkers in both the scatter plots of being able to make that connection of part C. We think.

It really helped to further derisk the program.

Thank you and your next question comes from Michael Schmidt with Guggenheim. Please go ahead.

Hey, Good morning. This is Paul on for Michael Thanks for taking our questions I have one on your Iraq and then.

Operator: Thanks for taking our question. I have one on your iRacimid. You know, there's been some renewed focus recently on tolerability with the newer and more up-and-coming generation of IMIDS, particularly on neutropenia. So, just wanted to get a sense of your expectations around initial safety for 4.1.3, given how you've designed the molecule, and any read-through, if any, from the competitive landscape. And then, secondly, you know, you mentioned that 3.0 has some potential in inflammatory and fibrotic diseases.

There has been some renewed focus recently on tolerability with newer and more potent generation.

Particularly on neutropenia. So just wanted to get a sense of your expectations around initial safety equal 413, given how we've designed the molecule and any read through if any from the competitive landscape and then secondly, you mentioned that <unk> had some potential in inflammatory and fibrotic diseases I'm.

Operator: Just wondering if there's any gating factors that you're thinking about that's potentially initiating development outside of oncology, and if there's something we can expect if the PD and safety data from the Phase I look good. Yes, thanks, Paul.

Just wondering if there's any gating factors that you're thinking about potentially initiating development outside of oncology and there's something we can expect.

If the PD and safety data from the phase one bucket.

Yeah. Thanks, Paul.

Nello Mainolfi: So, great questions. So, the first one, I'll just share some thoughts. So, every, I think everybody's well aware of the pharmacology of PIMIDs.

So great question. So the first one.

I'll just share some thoughts.

So I think everybody's well aware of the pharmacology of the image.

Nello Mainolfi: I think we're well aware of the strategies that Celgene, or now Briscoe, has taken to develop those drugs. So I'm personally not surprised by seeing the pharmacology of the image play out in different clinical studies, depending on the potency of the compound. And I think, as we've said in the past, our goal has been to maximize.., the synergistic pharmacology between the ARAC4 degradation and the IMID degradation in a way that we will be able to maximize activity while managing safety. And in fact, based on the potency, the pKa, the distribution profile of our molecules, we've optimized these molecules to be dosed once every three weeks, which is obviously very different than how images are dosed.

And our people are well aware of.

The strategies that celgene that.

Or now Bristow has taken to develop those drugs. So.

I am personally.

Not.

Surprised by.

Seeing the pharmacology of the Miss play.

Play out in different clinical studies, depending on the potency of the compound and I think as we've said in the past.

Our goal has been to maximize.

The synergistic pharmacology between the Iraq, Iraq for degradation and the EBIT degradation in a way that we would be able to maximize.

Activity while.

Managing safety and in fact, we.

<unk>.

Based on the potency the PK the distribution profile of our molecules we bought demised.

This molecule to be dosed once every three weeks.

Which is obviously very different than how image R. R.

Nello Mainolfi: So we feel very confident going into the study that we'll be able to really explore and understand how the preclinical study will translate into clinical, both safety and activity. And we believe that we spend a lot of time running non-human primate studies to really understand how to walk the line between efficacy and safety. So we're confident going into the study. And again, before the end of the year, we will be updating everybody on how the data is evolving. On the stat tree...

So we feel very confident going into the study.

We'll be able to really explore and understand how the preclinical studies will translate into clinical both safety and activity.

And we believe that we spend a lot of time running nonhuman primate study to really understand how to walk the line between efficacy and safety. So we're confident going into the study and again before the end of the year we will.

We will be updating.

Everybody on how the data is evolving on the statutory.

Nello Mainolfi: So we've invested heavily on their program. There was a nice review the other day out there on all the other efforts that are in the space. And I think it's probably fair to say that our selective degrader is probably the most de-risked approach to targeting selectively and specifically STAT3. We also spent, I would say, you know, a couple of years actually under trying to fully understand the pharmacology and safety of STAT3 degradation, running multiple efficacy and safety studies across many type of disease states.

So we've.

We've invested heavily on the program.

There was a nice review the other day out there on all the other efforts that.

In the space and I think it's probably fair to say that our selective degree there is probably the most de risked approach to targeting selectively and specifically three we also.

Spend I would say a couple of years actually.

I'm, just trying to fully understand the pharmacology and safety of SER three degradation.

Running multiple efficacy and safety studies across many type of disease States.

Nello Mainolfi: And so the reason why we've separated oncology from non-oncology indications is because we have come to the conclusion that the degradation profile needed in oncology is actually quite different than the degradation profile needed outside of oncology. And so the reason why a molecule that will be developed outside of oncology is our, slightly behind is because we're, again, firming up the PKPT safety to then advance that approach towards the clinic. So I don't know if that's a satisfying answer, but that's really the story to the STAT3 program right now.

So the reason why we've separated oncology from non oncology indications is because we have come to the conclusion that the degradation profile needed oncology is actually quite different than the degradation profile needed outside of oncology and so the reason why.

Molecules that will be developed outside of oncology as our.

Slightly behind it because we're again firming up the PK PD safety today in advance that approach towards the cleaning so.

I don't know if thats, a satisfying answer, but that's really the story to the <unk> three program right now.

Thank you. Your next question comes from Vikram <unk> with Morgan Stanley . Please go ahead.

Operator: Thank you. Your next question comes from Vikram Purohit with Morgan Stanley. Good morning everyone, this is Gospel on Forum. Vikram, we have two questions. The first one pertains to Stanofy.

Nello Mainolfi: Could you walk us through the mechanics of how your decision making process with Stanofy will unfold? following the release of the AT474 data in second half of 2022. Specifically, I mean, how long does Sanofi have to review the package and how will you be working with them to prioritize the indication to evaluate in phase two? And when do you think this discussion could be provided to the street?

Good morning, everyone. This is <unk> on for Vikram.

We have two we have two questions. The first one pertains to San Jose I mean.

Could you walk us through the mechanics of how your decision making process with Senator will unfold.

Following the release of the.

For some important data.

Second half of 2022.

Specifically I mean, how long does kind of you have to review the package.

How would you have been working with them characterize indication too.

Evaluate in phase II.

And when do you think this could be provided to the street.

Nello Mainolfi: and then how are you thinking about the timing and process for your opt-in decision. Thanks. Okay, thanks. So, first question, what's the process? So, as we've shared in the past, and I think it's changed, we are in very close communication with our partners. We do that with every one of our partners.

And then how are you thinking about the timing and process for opt in decision.

Thank you.

Okay. Thanks.

So.

So first question, what's the process so as we've shared in the past.

This change so when we we are in very close communication with our partners. We do that with every every one of our partners and so they are obviously, well aware and they're part of key.

Nello Mainolfi: So, they're obviously well aware and they're part of key, whether it's a regulatory interaction or an internal decision. And so, when we complete, when we will complete the patient cohort that we just described that we've extended to generate even more data, I strongly believe to generate hopefully key de-risking data, then we will be very quickly presenting Sanofi with a full data package, which, just to remind everybody, includes all preclinical as well as Phase I data. So, it's actually a large, large document.

Whether it's the regulatory interactions or an internal decision.

And so we when we complete when we will complete the patient cohort that we just described that we've extended to generate even more data I strongly believe to generate hopefully keep derisking data.

Then we will be very quickly.

Presenting incentive fee with the with the full data package. We just to remind everybody includes all preclinical as well as phase one data. So it's actually a large large documents and then we haven't disclosed how many days, but they have X number of days.

Nello Mainolfi: And then, we haven't disclosed how many days, but they have X number of days. It's not like half a year, it's definitely less than that, to make the decision of whether to advance 474 into Phase 2. We expect that, at least our firm goal is to present that complete data set to Sanofi before the end of the year, and then hopefully that decision will be swift as, again, they're up to date with all the development of the program.

It's not it's not like half a year, it's definitely less than that.

To make the decision of whether to advance 474 into phase two.

We expect that.

At least our firm goal is to present that complete dataset <unk> before the end of the year and then hopefully that decision will be swift as again they are up to date with all the development of the program.

Nello Mainolfi: And again, I think there was a question about Kymera's opt-in, if I understood well. And so the mechanism for that is, if and when, hopefully, Sanofi decides to advance KT474 into a randomized placebo-controlled Phase 2 study or multiple Phase 2 studies, then at the end of the first one, with proof-of-concept study in hand, Kymera will have the opportunity to decide if we want to co-develop and co-commercialize in the U.S., sharing profit and losses 50-50.

Then I think there was a question about <unk> opt in if I.

Understood well.

And so that will the mechanism for that.

If and when hopefully, Tennessee decides to advance <unk> 474 into a randomized placebo control phase two study or multiple phase two studies.

Then at the end of the first one.

Proof of concept study in hand.

Canada will have the opportunity to decide if we want to co develop and cocoa Michelle lives in the U S sharing profit and losses 50, 50 and that decision will have to be made before the beginning of phase III. So that we can operationally and financially contribute.

Nello Mainolfi: And that decision will have to be made before the beginning of Phase 3, so that we can operationally and financially contribute to Phase 3 studies. Thank you. Your next question comes from Kalpit Patel with Be Riley, please go ahead. Yes, hi, good morning.

Two phase III studies.

Well thank you.

Your next question comes from Pete <unk> with B Riley. Please go ahead.

Yes, hi, good morning, and thanks for taking my question.

Operator: And thanks for taking my question. One, just one question on your IRAC admit program. I think another drug developer curious, have had a clinical hold place recently on their IREC-IV inhibitor on safety concerns for RABDO. I guess, does that in any sense impact your thinking about how you're advancing this IREC-AMID Program? You know, from my understanding that Qiis drug is more of a dirty kinase inhibitor that might've been responsible for the safety concerns, but do you have any evidence of elevated, you know, CK levels in your preclinical studies with the IREC-AMID Program? Yeah, thanks for the question. No, I think it's a good question.

One just one question on Iraq.

Iraq and mid program I think another drug developer curious.

Had a.

Clinical hold placed recently.

<unk> four inhibitor on safety concerns for Raptor.

I guess does that in any impact.

Impact your thinking about how you are advancing this Iraqi mid program.

From my understanding that that curious as drug is more of a dirty kinase inhibitor.

There might have been responsible for the safety concerns, but do you have any evidence of elevated CK levels in your preclinical studies with the Iraq in the program.

Yes, thanks for the question.

Jared Gollob: I think as you mentioned, you know, the curious compound, you know, is a multi-kinase inhibitor. And in addition to IRAC4, one of its key targets is FLIP3. And there have certainly been published reports of rhabdomyolysis occurring with other FLIP3 inhibitors. So we think it's highly likely that the rhabdomyolysis that they're seeing and that's problematic and potentially dose-limiting for them is because of the FLIP3 targeting. With regard to IRAC4 targeting, you know, we and others have not seen any rhabdomyolysis with either IRAC4 targeting or the use of Arachamid in our preclinical studies. You know, as you know, in our IRAC4, you know, phase one, you know, we are engaging the target quite robustly and knocking out the target by 98%. You know, we have not seen any rhabdomyolysis.

I think it's a good question I think as you mentioned, but curious compound is a multi kinase inhibitor.

In addition to Iraq for one of its key targets is split three.

<unk> certainly been.

Public reports of Rhabdomyolysis occurring with other flip three inhibitors. So we think it's highly likely that the rhabdomyolysis that theyre seeing and thats problematic in potentially dose limiting for them is because of the flip for targeting with regard to Iraq, we're targeting we and others have not seen any rapid biolysis without the Iraq war targeting where they use.

If Iraq made in our preclinical studies.

As you know in our Iraq for Phase one we are engaging the target quite robustly at knocking down the target by 98% and we have not seen any any rhabdomyolysis. We're not aware of any reports of rhabdomyolysis from Pfizer, whether Iraq, where kinase inhibitor in their various clinical trials.

Jared Gollob: We're not aware of any reports of rhabdomyolysis from Pfizer with their IRAC4 kinase inhibitor in their various clinical trials. And as you also probably know, you know, there are IRAC4 null individuals, you know, who as adults really have no clinical phenotype and certainly have no muscle pathology. So we don't think that there's a connection between IRAC4 targeting and rhabdomyolysis. And that's what CURES is seeing again is probably due to off-target effects and most likely FLIP3 targeting.

And as you also probably know.

There are Iraq toward an all individuals who has adult really have no clinical phenotype and certainly have no muscle pathology. So we don't think that there is a connection between Iraq for targeting in Rhabdomyolysis and Thats. What you are seeing again, it's probably due to off target effects and most likely flip re targeting.

Thank you.

Your next question comes from <unk> with Cowen and company.

Operator: Thank you. Your next question comes from Divya Rao with Cowen and, Unknown Speaker We've got our on-for-mark. Congrats on the update. Thanks for starting us off.

Yeah, Mark Congrats on the update.

First one is could you talk about what you do.

Operator: The first one is, could you talk about what you consider meaningful degradation for IRAC4 in the ADHS population? And then do you think the levels of IRAC4 needed to drive this meaningful clinical benefit is different between the two? And then just like a little bit more broadly, are you willing to comment on the venues you plan to present the updates on all three clinical updates coming later this year? Would it be like a medical meeting or possibly another R&D day? Thank you. Great. So, you broke up at a point, so I'm going to repeat the question.

Paul degradation for Iraq for in the ADHD population.

And then do you think the level of Iraq war needed to drive meaningful clinical benefit is different between the two.

And then just like a little bit more broadly are you willing to comment on the venues you plan to present the updates on all three clinical updates coming later this year.

Would it be like a medical meeting or possibly another R&D day.

Yeah.

Great So yeah.

You broke up at a point, so I'm going to repeat the question hopefully I got it right. So the first part was do you expect the degradation profile to needed to be different between the chest and I'll.

Nello Mainolfi: Hopefully, I got it right. So, the first part was, do you expect the degradation profile to need to be different between HS and AD? I'll let Jared take that one, and then I want to answer the presentation venues. So, we have always said that we like to present scientific data at scientific or medical meetings. We've also said that our commitment to timelines, And again, going back to the point that I made about transparency and credibility, it's paramount.

I'll, let Jerry I'll take that one and then I want to answer the presentation venues. So we have always.

<unk> said that we like to present scientific data at.

Scientific or medical meetings, we've also said that our commitment to timeline.

And again going back to the point that I made about transparency transparency and credibility is paramount.

Nello Mainolfi: So if we said that we're going to present the data before the end of the year, which is true for all three programs, we're going to try our best to do it in a medical meeting. If not, if for timeline reasons of abstract omission, et cetera, we won't be able to do it, then we'll find another venue, whether it's an R&D day or it's a focus meeting. It's not our preference by far, but again, I just want to say that as a company, we like to commit to the timelines that we give, unless obviously some operational issue arises and we can't deliver on the timelines, which is not the philosophy we have at Kymera. Jared, do you want to comment on the degradation profile? Yeah, yeah, I think it's a really important question.

Said that we're going to present that data before the end of the year, which is true for all three programs.

We're going to try our best to do it in a medical meeting if not.

For timeline reasons of abstract submission et cetera.

We won't be able to do them would find another venue, whether it's an R&D day or is it focused meeting it is not our preference.

But again.

I just want to say that as a company, we like to commit to the timelines that we gave out less obviously some operational issue arises and we can deliver on the timelines, which is not the philosophy, we have a camera.

Jerry do you want to comment on the degradation profile, yes, yes, I think it's a really important question I think that we anticipate that the degradation that we need.

Jared Gollob: I think that we anticipate that the degradation that we need for clinical impact, you know, should be similar for AD and HS. You know, we've learned from our, you know, preclinical mechanistic models of inflammation that 85% or greater degradation really has an impact on inflammation and the induction of various torrent inflammatory cytokines that drive inflammation. We've also learned from our phase one, you know, healthy volunteer study so far that a similar threshold, 85% or greater degradation is associated with an impact on ex vivo cytokine induction.

The impact should be similar for AE in Hs, we've learned from our preclinical mechanistic models of inflammation that 85% or greater degradation really has an impact on inflammation in the induction of various tour inflammatory cytokines that drive information. We've also learned from our phase one healthy volunteer studies.

Far that similar threshold, 85% or greater degradation is associated with an impact on ex vivo cytokine induction. So we think that really what's important is how much degradation as needed to impact the function of the <unk> pathway and importantly, a bunker that we're interested in is the.

Jared Gollob: So we think that really what's important is how much degradation is needed to impact the function of the TLR-ILR1R pathway and importantly, you know, the particular function that we're interested in is the induction of inflammatory cytokines and chemokines.

Induction of clinical laboratory cytokines, and chemo kinds and so we anticipate a similar threshold of lockdown at least 85% or greater.

Jared Gollob: So we anticipate a similar threshold of knockdown, at least 85% or greater, you know, in blood and in skin for us to really be able to impact inflammation in both of these diseases. And we feel from what we've seen so far in the healthy volunteer study with the dose that we plan on taking into Part C, that we should be able to readily attain those levels of IRAC-4G. Thank you. Your next question comes from Eric Joseph with JP Morgan. Please go ahead. Hi, good morning.

Blood and scan for us to really be able to impact inflammation in both of these diseases that we feel from what we've seen so far in the healthy volunteer study with a dose that we plan on taking into part C that we should be able to readily to attain those levels of Iraq for degradation.

Operator: Thanks for taking the questions. I wanted to revisit the first question on QT, specifically the dose levels, where you observed the extension or the prolongation, and how it resolved. I guess, did it resolve on consistent dosing, or was dosing modified in any way? And do you anticipate having to conduct a thorough QT study as part of a Phase I package prior to handover to Snowden? Thanks Eric, great question. I think it's great an opportunity to clarify this point. So I just want to clarify one thing and then I'll pass it to Jared.

Thank you. Your next question comes from Eric Joseph with Jpmorgan. Please go ahead.

Hi, good morning, Thanks for taking the questions.

Hi.

Let's revisit the first question Mark.

Specifically the dose levels, where you observed.

The extension of the prolongation.

And how it resolved I guess resolved on consistent with dosing modified in any way.

Do you anticipate having to conduct.

A thorough Qt study as part of the base package.

Yeah.

Thanks, Eric Great question, I think it's great an opportunity to clarify this fall and so I'll just want to clarify one thing and then I'll pass it to Jerry So I think what we've said that this is.

Nello Mainolfi: So I think what we've said that this is a... Non-Dose Responsive, Step-Limiting, Modest-Finding, that never became an adverse event, not even a great one for QTC. And again, I'll repeat, the reason why we're sharing it is for being transparent as a company. Maybe, Jared, you can comment on.., those adjustments, resolution and all that stuff. Yeah, I think importantly, you know, during the conduct of the SAD and MAD, again, there were no ECG adverse events. There were no changes in QTC interval that rose to the level of being an adverse event.

Non dose responsive separately meeting modest fine being.

That never became an adverse event not even a great one for TTC and again I'll repeat the reason why we're sharing it is for being transparent as a company.

Maybe Joe you can come in on those.

Those adjustments resolution.

Yeah, I think importantly during the conduct of the Sandy.

Again, there were no.

Adverse events there were no changes in UTC interval that rose to the level of being an adverse event that was only after we completed those parts and then undertook a more thorough analysis of ecg's prior to selecting the dose part C that we noted.

Jared Gollob: It was only after we completed those parts and then undertook a more thorough analysis of ECGs prior to selecting the Dozer Part C, that we noted this modest... Prolongation. Again, that was not adverse. I think importantly, as I mentioned earlier, you know, this was not associated with prolongation that reached any sort of threshold that would be associated with arrhythmia. I think it's also important to note, you know, as we said, in order to be open and transparent with FDA, you know, we did share these data with them and, you know, we, you know, have to go ahead to go into Part C with a very robust dose, 100 milligrams, that should help us to really maximize pharmacology.

This modest.

Qt prolongation again that was not adverse.

I think importantly, and as I mentioned earlier. This is not associated with prolonged <unk> reached any sort of thresholds that would be associated with Arhythmia. I think it's also important to note as we said in order to be open and transparent with FCA, we share these data with them.

And we have the go ahead to go into part C. With a very robust dose on a milligram that should help us to really maximize pharmacology, we're continuing with daily dosing, where notwithstanding dosing at 28 days and including clinical endpoint I think in terms of your question around whether we need a thorough Qt study I mean, it's very common for.

Jared Gollob: We're continuing with daily dosing. We're now expanding dosing to 28 days and including clinical and... I think in terms of, you know, your question around whether we need a thorough QT study, I mean, it's very common for, you know, companies to do thorough QT studies. Sometimes the TQT studies can be bypassed by, you know, having enough ECG information from your phase one study to be able to determine whether there is any sort of QT effect.

Sure.

<unk> to do thorough Qt studies, sometimes DT Qt studies can be bypassed by having enough ECG information from your phase one study.

To be able to determine whether there is any sort of qt effect. It is a possibility that we might do a thorough Qt study I think that will depend in the future of what we see in part C.

Jared Gollob: It is a possibility that we might, you know, do a thorough QT study. I think that will depend in the future on what we see in Part C, but I think that certainly is on the table, but at least we have some understanding right now that, you know, whatever QT effect we're seeing, you know, is very modest and currently is not being, has not met the threshold for being adverse. Thank you.

But I think that certainly is on the table, but at least we have some understanding right now that whatever qt effect were seeing.

Very modest and they currently is not being.

Met the threshold for being adverse is not even close to that.

Thank you. Your next question comes from Richard Law with Credit Suisse. Please go ahead.

Jared Gollob: Your next question comes from Richard Law with Credit Suisse. Hi, good morning. I have two questions. So regarding the QTEC observation, did the FDA ask for any mitigation plans that we occur again? And at what point would that trigger some sort of intervention?

Hi, Good morning, I have two question so regarding the Qt observation.

They asked for any mitigation plans that we occur again.

At what point would that trigger some sort of intervention.

Operator: And then the second question I have is that on KT474, can you share with us any updated changes to timeline or any preliminary discussion you have with Sanofi regarding the Phase 2 plans, like in terms of what type of patients will you be exploring? And also you mentioned the RCT trials, would that be any head-to-head studies with biologics? Thank you. Yeah, no, thanks. I just want to clarify, again, the first point. So, we actually did not have to share this.

Then the second question I have is that on K T. 474 can you share with us any updated changes to timeline or any preliminary discussion you have with Santa Fe regarding the phase two plan.

You've heard about what type of patient for U B S.

Flooring and also you mentioned the RCT trials would that be any head to head study with biologics. Thank you.

Yes. Thanks.

Just wanted to clarify again, the first Boeing so we actually did not have to share. These Q2 see finding with FDA, but we decided to do we have a really strong relationship our regulatory group is really strong.

Nello Mainolfi: Joseph, We have a really strong relationship, our regulatory group is really strong, we've had almost four, close to four IMD submissions, several other follow-ups, so we try to be also, as we do also with FDA, transparent and collaborative. We obviously had to engage them to amend the protocol, and when we did, we also submitted all the safety, PK, PD, and all the data that we generated. We really didn't receive.., you know, much of comments with regards to how we're I think they generally align with our proposed plans and there was no particular mitigation plan that was discussed.

For almost for close to four Anda submission several other falloff so.

We tried to be also as we view also with SDA transparent and collaborative.

We obviously had to engage them to amend the protocol and when we did we also submitted all the safety PK PD.

Data that we generated we really didn't receive.

Much of comments with regard to how we are.

How we're proposing we.

We continue to explore the safety of the drive it.

Generally align with that proposed plans and there was no.

Particular mitigation plans that was discussed this was.

Nello Mainolfi: This was our study design protocol and there was a general alignment in the big picture. With regard to Sanofi, we again, we are very close to the team, to the development team and, I think where we are today is that, as we've always said, we have some really high-priority indications. There are several, but what we've discussed often is HS, AD, RA, you know, we talked last week a lot about lupus, for example.

The study design protocol and there was a general alignment in the Big picture.

With regards to sign a fee.

We again, we have.

Very close to the team to the development team and.

I think where we are today is that as we've always said, we have some really high priority indications.

There are several.

We've discussed often is the chest.

<unk>.

Hey.

We talked last week a lot about Lucas for example.

And I think what we agree and it makes sense. We are both data driven companies. We will continue to see how data emerge from these patient study obviously now this patient studies much more powered.

Nello Mainolfi: And I think what we agree, and it makes sense, we're both data-driven companies. We will continue to see how data emerge from this patient study. Obviously, now this patient study is much more powered in terms of data that we generate, and I think with that data in hand, we will refine the strategy and the selection for the right dose, sorry, for the right priorities that we'll have for phase two and beyond. Thank you. Your next question comes from Shi Qiang Xu with Berenberg.

Terms of data that we generate and I think with that data in hand, we will refine the strategy and the selection for further write those sorry for the right priorities that will we will have for phase two and beyond.

Thank you. Your next question comes from Steve <unk> with Baird. Please go ahead.

Great. Thank you.

Operator: Great, thank you. I have two questions. First one on the Step 3 program. In the past, you have communicated potential accelerated rate approvals from UCL, I guess based on the data you've seen, or have you continued to hold that view? And also on that program, I see you have amended the protocol to include a combo study. Can you, Discuss more, provide more color on how you want to go with that.

Two questions first one on the <unk>.

That's a great program.

In the past you have communicated potential accelerant for hosting army.

Now I guess based on that.

The data that you're seeing or.

Okay.

Oh that view and also on that program.

I see you have amended the protocol to include.

I'm both study.

Yeah.

Discuss more probably more color on how you want to go with that.

Yes.

Yes, it was a bit noisy, but I think the question was.

Jared Gollob: Yeah, it was a bit noisy, but I think, Jared, the question was what is the path to potential accelerated approval that we were planning with STAT3 and then the combo, like what is the plan on how to develop the combo? Yeah, I think in STAT3, you know, we see rapid development opportunities in STAT3-dependent hemo-legacies, especially... T-cell malignancies like peripheral T-cell lymphoma, Mosquino treatment, because these are areas with very high unmet medical need, we think there are rapid approval or accelerated approval opportunities with our staph 3 degrader. Prieta, Mono Therapeut, In terms of combination, we tend to think more about combination in solid tumors where we have shared very interesting data where the immunomodulatory properties of STAT3 synergize with anti-PD-1 drugs.

What is the path to potential accelerated approval that we are planning with three and then the combo like what is the plan on how can benefit them.

Step three we see rapid development opportunities.

Thats very dependent hemolytic disease, especially certain T cell malignancies like peripheral T cell lymphoma.

Cutaneous T cell lymphoma, and LVL leukemia, where you tend to see activating mutations that were in Jacksonville, or even just hyper activation of the pathway to a preclinical animal model data, where we've seen very robust.

Tumor activity with staff reader greater as a monotherapy and because these are areas of very high unmet medical need we think there are rapid approval or accelerated approval opportunities.

Our SATA three integrated <unk> three as a mono therapy in terms of combination and we tend to think more about combination in solid tumors, where we have shared.

Interesting data.

Where the immuno market worry properties at three.

Synergizes with anti PD one drugs.

Jared Gollob: Martha Freels Cagny Engineering, Kl importance, Adrian empress这是个技术的事业在科学学院发展中, Such as colorectal cancer. So we think there could be an even larger opportunity for combination containing Pac killing marinermaist 可以在有充粹的病理程序中生出一种具有细析感染觉知循环 û物体细极的 annoyed atympanum activity culminating in科学学院中国的新机能。 Perhaps, although we think that there will be an even larger opportunity for combination development with checkpoint timbre inside with solid tumors,环境领域的环境问题和病变及症状的发展方式都可能更加非常大。 The past, you know, may not be as exhilarated because it was a combination of studies as monotherapy path, but we think that those are also very attractive and represent even larger opportunities. Great, thank you. Maybe you guys can follow up there, battery, and it.

To show sort of synergistic anti tumor activity in various solid tumor models in generic tumor models, such as colorectal cancer. So we think there could be an even larger opportunity for combination development with checkpoint inhibitors in solid tumors. Those past may not be as accelerated because of the combination studies as monotherapy path, but we think that those are also.

Very attractive and represent even larger opportunities a integrator.

Great. Thank you.

All up there.

Hum.

Accurate and.

And also you have Iraq in Med program have you seen I know it's early days have you seen any Qt C.

Operator: [inaudible] and also your IRAC Inmate Program. Have you seen, I know it's early days, have you seen any QDC findings in those programs? Yeah, so far we're early in, we just opened our phase one, so we're not in possession of any human safety data. Generally, what I would say is that, you know, QTC prolongation is not...

The findings in those programs.

Yes, so so far we're early in.

Just open a phase one so we were not in possession of any human safety data generally what I would say is that Q T C.

Foundation is not the signal that we've had to deal with within our pipeline. So it's not something that.

Jared Gollob: The link is being shared at telegithum.org, is present in our Portfolio Molecules project. Thank you, and I'm not showing any further, Thank you. I would like to turn the call back to Nello Mainolfi for his final remarks. Yeah, so thank you.

Is present in.

In our in our.

Portfolio molecules broadly.

Thank you and I'm not showing any further questions in the queue I would like to turn the call back to Nello <unk>.

For his final remarks, yes. Thank you first I want to thank everybody for tuning in today I realize it was a very busy day.

Nello Mainolfi: First, I want to thank everybody for tuning in today. I realize it was a very busy day in the biopharma space in terms of calls. So thanks for calling in. I just want to reiterate, we're a company that is... Almost six years in, we have a rich pipeline of programs across a variety of indications. Again, we've talked about HSAP, T-cell lymphoma, T-cell leukemia, solid tumor, diffuse rash with cell lymphoma, and then soon with MDM-II, other indications.

In the in the Biopharma space in terms of calls so thanks for calling in.

When I reiterate so we're a company that is.

Almost six years in we have a rich pipeline of programs across a wide variety of indications again, we've talked about HSA at the T cell lymphoma T cell leukemia solid tumor diffuse large b cell lymphoma.

And then soon with MDM to other indications. So you see that we're obviously a company that is trying to build into a fully integrated business that peaks protein degradation into the space, where it should be which is really changing people's lives.

Nello Mainolfi: So you see that we're obviously a company that is trying to build into a fully integrated business that takes protein degradation into the space where it should be, which is really changing people's lives. We're here for any follow-up, for any questions that others might have during the day or in the next few days. I want to thank the team here, Bruce and Jared, and the team at Chimera for continuing to generate really best-in-class data every quarter, and wish everybody a good day. Thank you, ladies and gentlemen, for participating in today's call. You may now disconnect. Have a wonderful day. [music]

We're we're here for any follow up for any questions that others might have during the day or in the next few days and want to thank the team here, Bruce and Jared into T. Mec Humira for continuing to generate really best in class data every quarter and.

We should everybody a good day.

Thank you, ladies and gentlemen for participating in today's call. You may now disconnect have a wonderful day.

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