Q2 2021 Shattuck Labs Inc Earnings Call

August 11, 2021

[music].

Operator: Good afternoon, everyone, and welcome to Shadak Labs' second quarter financial results and business updates call. Today's call is being recorded at this time. I would like to turn the call over to Connor Richardson, Senior Director of Finance and Investor Relations at Shatak.

Good afternoon, everyone and welcome to Shaddock Labs second quarter financial results and business update call. Today's call is being recorded at this time I would like to turn the call over to Conor Richardson Senior director of Finance and Investor Relations of genetic labs.

Conor Richardson: Thank you, operator. Good afternoon, everyone, and welcome to the Shattuck Labs conference call to discuss our second quarter financial results and business update. The press release for our financial results was issued after market close this afternoon and can be found in the events and presentations section of our website, shaddocklabs.com. During this afternoon's call, the Shattuck team will provide a business overview of the second quarter of 2021, including an update on our clinical development plans for SL 172154 and SL 279252. A Q&A session will follow our prepared remarks.

Thank you operator.

Good afternoon, everyone and welcome to the Shattuck Lab's conference call to discuss our second quarter financial results and business updates. The press release for our financial results was issued after market close this afternoon and can be found on the events and presentations section of our website Shattuck.

<unk> Dot com.

During this afternoon's call Shattuck team will provide a business overview of the second quarter of 2021.

Including an update to our clinical development plans for S. L 107 to 154 and S. L 279 to five two.

A Q&A session will follow our prepared remarks joining.

Conor Richardson: Joining me on the call today are Dr. Taylor Shriver, our chief executive officer, Dr. Linne Pandeet, our chief medical officer, Andrew Neal, our chief financial officer, and Casey D. Young, our chief business officer. Before we begin, I would like to remind you that today's webcast contains forward-looking statements, within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements represent management's judgment as of today and may involve certain risks and uncertainties that could cause actual results to differ materially from those expressed in or implied by these statements.

Joining me on the call today are Dr. Taylor Schreiber, our Chief Executive Officer, Dr. Linda <unk>, our Chief Medical Officer, Andrew Neil Our Chief Financial Officer, and Casey, Dr. Our Chief business Officer.

Before we begin I would like to remind you that today's webcast contains forward looking statements within the meaning of the safe Harbor provisions of the private Securities Litigation Reform Act of 1995.

Such statements represent management's judgment as of today and may involve certain risks and uncertainties that could cause actual results to differ materially from those expressed in or implied by these statements.

Conor Richardson: For more information on these risks and uncertainties, please refer to our most recent annual report on Form 10K for the year ended December 31st, 2020, and our other filings with the SEC, which are available from the SEC's website or on our corporate website, shoddicklabs.com. Any forward-looking statements represent our views as of today, August 11, 2021. With that, I will now turn the call over to Taylor Shriver, our chief executive officer. Thank you, Connor.

For more information on these risks and uncertainties. Please refer to our most recent annual report on Form 10-K for the year ended December 31, 2020, and our other filings with the SEC.

Are available from the SEC's website or on our corporate website Shattuck labs dot com.

Any forward looking statements represent our views as of today August 11.2021.

With that I will now turn the call over to Taylor Schreiber, our Chief Executive Officer Taylor.

Taylor H. Schreiber: Good afternoon, everyone, and thank you for joining us. Today's earnings call is the first since our initial public offering in October of 2020, and I am exceptionally proud of the milestones our team has achieved since that time. Our clinical team has done an outstanding job of advancing the clinical development of both SL172154 and SL279252, our clinical stage agonist redirected checkpoint or arc compounds. As a reminder, 172154 is a SERP Alpha FCCC-C-D-40 ligand, bi-functional fusion protein currently in two different phase one clinical trials, one for patients with advanced ovarian cancer and another for patients with squamous Our second clinical stage compound, 279252, a PD1-FC-Ligand bi-functional fusion protein, is being developed in collaboration with Takeda Pharmaceuticals and is in phase one development for patients with advanced solid tumors.

Thank you Conor and good afternoon, everyone and thank you for joining us.

Today's earnings call is the first since our initial public offering in October of 2020, and I am exceptionally proud of the milestones our team has achieved since that time.

Our clinical team has done an outstanding job of advancing the clinical development of both sell one seven to 154 and fell to 795 to our clinical stage agonist redirected checkpoint or arc compounds.

As a reminder, one seven to 154 as a surf Alpha F. C. C. D 40 ligand bifunctional fusion protein currently in two different phase one clinical trials, one for patients with advanced ovarian cancer.

And another for patients with squamous cell carcinoma of the head and neck or skin.

Our second clinical stage compound to 795 to a PD one FC Ox 40 ligand bifunctional fusion protein is being developed in collaboration with Takeda Pharmaceuticals and is in phase one development for patients with advanced solid tumors.

Taylor H. Schreiber: Both of our ARC product candidates are first-in-class compounds that entered the clinic in less than four years since our founding due to the pioneering work of our scientific, manufacturing, and regulatory teams. We are currently generating clinical data to validate the concept behind the ARC platform, and we are particularly excited to share this clinical progress with you in just a few months. Specifically, we have submitted our clinical data from the monotherapy dose escalation portion of our phase one clinical trials for 17254 and 279252 to the Society for Immunotherapy of Cancer, also known as SITC, for presentation at its annual meeting on November 10th through, Emerging data During 2021, we have made steady progress towards advancing the dose escalation cohorts for 172154 in patients with relapsed or refractory ovarian cancer.

Both of our arc product candidates are first in class compounds that entered the clinic in less than four years since our founding due to the pioneering work of our scientific manufacturing and regulatory teams.

We are currently generating clinical data to validate the concept behind the arc platform and we are particularly excited to share. This clinical progress with you in just a few months time.

Specifically, we have submitted our clinical data from the monotherapy dose escalation portion of our phase one clinical trials for one seven to 154 and $2.795 two.

So the society for immunotherapy of cancer also known as <unk> for presentation at its annual meeting on November 10th through 14th.

Emerging data has guided us to amend and expand our clinical trials and today, we will provide some context for those expansions. In addition to our general corporate update.

During 2021, we have made steady progress towards advancing the dose escalation cohorts for one seven to 154 in patients with relapsed or refractory ovarian cancer.

Taylor H. Schreiber: We are pleased by the safety and tolerability profile observed thus far and are continuing to dose escalate into the higher dose level cohort. Given the totality of the data to date, we have begun to execute on our strategy to broaden clinical development into hematologic malignancies. Specifically, we will soon initiate a clinical trial for patients with acute myeloid leukemia, including a TP53 mutant acute myloid leukemia cohort, as well as for patients with higher-risk myeloplastic syndrome.

We are pleased by the safety and Tolerability profile observed thus far and are continuing to dose escalate into the higher dose level cohorts.

Given the totality of the data to date, we have begun to execute on our strategy to broaden clinical development into hematologic malignancies.

Specifically, we will soon initiate a clinical trial for patients with acute myeloid leukemia, including a T. P 53 mutant acute myeloid leukemia cohort.

As well as for patients with higher risk Myelodysplastic syndrome.

Taylor H. Schreiber: We see an opportunity for 172154 to potentially emerge as a best-in-class compound for these patient populations. We have also made significant progress in our clinical development efforts for 279252. We have completed enrollment through the 6 milligrams per kilogram dose level, evaluated both weekly and biweekly dosing schedules, and gained enormous insights regarding the behavior of ARC compounds in patients with cancer. The available data suggest that there is a compelling scientific rationale for continued dose escalation beyond our originally contemplated top dose level of 6 milligrams per kilogram, which Linney will expand on in a few moments.

We see an opportunity for 170.154 to potentially emerge as a best in class compound for these patient populations.

We have also made significant progress in our clinical development efforts for $2.790 252.

We have completed enrollment through the six milligram per kilogram dose level.

Evaluated both weekly and biweekly dosing schedules and gained enormous insights regarding the behavior of arc compounds in patients with cancer.

The available data suggests that there is a compelling scientific rationale for continued dose escalation beyond our originally contemplated top dose level of six milligrams per kilogram, which linear will expand on in a few moments.

Taylor H. Schreiber: Turning to our corporate update, it is my pleasure to introduce Dr. Abanov Shukla, who joined us this quarter as our chief technical officer. Dr. Shukla has held both technical and leadership roles at large pharmaceutical companies, contract manufacturing organizations, and small biotechnology companies. He brings a wealth of experience to our growing biologics manufacturing team. Abanov's experience across the full spectrum of biologics manufacturing is a critical advantage as we continue to build our internal capabilities.

Turning to our corporate update it is my pleasure to introduce Dr. <unk> <unk>, who joined US this quarter as our Chief Technical Officer.

Spinoff has helped both technical and leadership roles at large pharmaceutical companies contract manufacturing organizations and small biotechnology companies.

He brings a wealth of experience to our growing biologics manufacturing team.

<unk> experience across the full spectrum of biologics manufacturing is a critical advantage as we continue to build our internal capabilities I am very pleased to welcome <unk> to our executive team.

Today's call will discuss select clinical data from our <unk> platform, which we plan on unveiling in greater detail at <unk> later, this year as well as insights into our clinical strategy.

Lenny will discuss our clinical development programs to date.

And then Andrew will provide the financial update for the second quarter of 2021, and then I'll be back for some concluding comments.

Taylor H. Schreiber: I am very pleased to welcome Abinov to our executive team. Today's call will discuss select clinical data from our ARC platform, which we plan on unveiling in greater detail at SITSI later this year, as well as insights into our clinical strategy. Lenny will discuss our clinical development programs to date, and then Andrew will provide the financial update for the second quarter of 2021, and then I will be back for some concluding comments. With that, I will now turn the call over to Linnie Pandit, our chief medical officer.

With that I will now turn the call over to Linda <unk>, Our Chief Medical Officer Lenny.

Thank you Taylor and good afternoon, everyone.

I would like to discuss our lead clinical program <unk> seven to 154, which is a step outside FC CD 40 ligand bifunctional fusion protein.

As of the mind that one seven to 154 contains the extracellular domain of the human <unk>.

Protein, which directly bind to and inhibit C. D 47.

In addition, and so one 7% to one five pool also contains the extracellular domain of the human CD 40 ligand protein the simultaneous skinny and directly activate the C. D 40 reset.

Arundathy Nirmalini Pandite: Thank you, Taylor, and good afternoon, everyone. First, I would like to discuss our lead clinical program, SL172154, which is a CERPALFA-CD40-like end, bi-functional fusion protein. As a reminder, SL172154 contains the extracellular domain of the human serp alpha protein, which directly binds to and inhibits CD-47. In addition, SR17254 also contains the extracellular domain of the human CD40 ligand protein to simultaneously and directly activate the CD40 research.

As most of you know we are currently exploring S. One seven to 154 in two ongoing phase one clinical trials.

Our first clinical study of <unk> seven to one type pool is a multi center open label dose escalation trial intended to assess the safety Tolerability pharmacokinetics antitumor activity and Pharmacodynamic effects.

Intravenous administration of <unk>, two wildfire pool as monotherapy in patients with relapsed refractory ovarian cancer.

Enrollment in the monotherapy dose escalation cohort has progressed smoothly.

Arundathy Nirmalini Pandite: As most of you know, we are currently exploring SL172154 in two ongoing phase one clinical trials. Our first clinical study of SL172154 is a multi-center, open-label, dose escalation trial intended to assess the safety, tolerability, pharmacokinetics, antitumor activity, and pharmacodynamic effects of intravenous administration of SL172154 as monotherapy in patients with relapsed, re Enrollment in the monotherapy dose escalation co-bots has progressed smoothly. We are currently completing enrollment at the fourth dose level of 3 milligrams per kilogram, and we plan to proceed to the next dose level of 10 milligrams per kilogram thereafter.

Currently completing.

And government at the full dose level of three milligrams per kilogram and we plan to proceed to the next dose level of 10 milligrams per kilogram thereafter.

Our second clinical trial of <unk> seven to one five pool is an ongoing multi center open label dose escalation clinical study intended to assess the safety Tolerability pharmacokinetics antitumor activity and Pharmacodynamic effects of intra Tumoral Ed.

Ministration of one seven to one five as monotherapy in patients with relapsed refractory squamous cell carcinoma of the head and neck or skin.

We remain on track to present initial data from this study in the first half of 2022.

Overall, we are very pleased with the emerging profile of <unk> one.

One seven to one fateful to date no dose limiting toxicities have been upset and either clinical trial and we are encouraged by our ability to dose in the higher dose level cohort.

Arundathy Nirmalini Pandite: Our second clinical trial of SL172154 is an ongoing multi-center, open-label, dose escalation clinical study intended to assess the safety, tolerability, pharmacokinetics, antitumor activity, and pharmacodynamic effects of intratumoral administration of SL172154 as monotherapy in patients with relapsed refractory squamousal carcinoma of the head and neck or skin.

Because instead of one 7% to one type pool contains both C. D 47 inhibitor B and C. D 40 agonists domains. The safety data should be considered in the context with prior C. D 40, 70 P B <unk> and.

<unk> C P 40 agonists.

On the C D 47th site consistent with our preclinical data we have not observed any evidence of anemia or thrombocytopenia, which we believe is due to the selection of an effective silent FC region, but it's still modest them into one platform we believe.

Arundathy Nirmalini Pandite: We remain on track to present initial data from this study in the first half of 2022. Overall, we are very pleased with the emerging profile of SL 172154. To date, no dose-limiting toxicities have been observed in either clinical trial, and we are encouraged by our ability to dose in the higher dose level cohort. Because SL172154 contains both CD-47 inhibitory and CD40 agonist domains, the safety data should be considered in the context of prior CD-47 inhibitors and CD-40 agonists.

This contributes to the safety profile and differentiate.

It sounds like 721 fateful from other C. D 47, anything because with active FC domains that have reported anemia or thrombocytopenia in clinical studies.

On the C. D 40 site. It is worth remembering that <unk> agonist antibodies have been in clinical testing for well over 20 years, but progress has been repeatedly has led by a combination of toxicities at low doses and evidence of a bell shaped dose response.

Good.

In the case of one seven to one five for clearing the three milligram per kilogram dose level would be a major milestone because previously studied C. D 40, agonists and content dose limiting toxicities, including a combination of cytokine release syndrome and liver dysfunction.

Arundathy Nirmalini Pandite: On the CD 47 side, consistent with our preclinical data, we have not observed any evidence of anemia or thrombocytopenia, which we believe is due to the selection of an affected silenced FC region for SL172154. We believe this contributes to the safety profile and differentiates SL17254 from other CD 477 inhibitors with active FC domains that have reported anemia or thrombocitopenia in clinical studies.

Auction above doses of roughly 0.3 milligrams per kilogram, which is 110th the current dose level of instead of one seven to one fateful.

To date, we have upset that none of these adverse events and we have observed unique evidence of C. D 40 engagement and Pharmacodynamic activity.

Arundathy Nirmalini Pandite: On the CD40 side, it is worth remembering that CD40 agonist antibodies have been in clinical testing for well over 20 years, but progress has been repeatedly hampered by a combination of toxicities at low doses and evidence of a well-shaped dose response curve. In the case of SL172154, clearing the 3 milligrams per kilogram dose level would be a major milestone because previously studied CD40 agonists encountered dose-limiting toxicities, including a combination of cytokine release syndrome and liver dysfunction at doses of roughly 0.3 milligrams per kilogram, which is one-tenth the current dose level of SL1.7. until 1.54.

Plan to share the details at the Citi Conference later this year.

We are very excited and encouraged by the emerging profile of <unk>.

One seven to 154 and believe that we have entered an immunologically active therapeutic window not seen with prior CD 40 at guidance.

The emerging profile of <unk>, one seven to one pipeful has prompted us to initiate our plans to reach an immunologically active dose from the phase one eight clinical trial in ovarian cancer to the phase one a one b clinical trial in hematologic malignancies.

Yes.

And to date, we are excited to announce that we plan to expand into clinical studies in both.

Acute myeloid leukemia and high risk Myelodysplastic syndrome.

Arundathy Nirmalini Pandite: To date, we have observed none of these adverse events, yet we have observed unique evidence of CD40 engagement and pharmacodynamic activities. We plan to share further details at the SITC conference later this year. We are very excited and encouraged by the emerging profile of SL 172154 and believe that we have entered an immunologically active therapeutic window not seen with prior CD40 agony. The emerging profile of SL 17254 has prompted us to initiate our plans to bridge an immunologically active dose from the Phase 1A clinical trial in ovarian cancer to the Phase 1A1B clinical trial in hematologic malignance.

In an email we plan to study <unk> seven to one fateful in combination with Azacitidine and we need to flex.

D P 52 mutant AML as.

As well as in higher risk Mds, we plan to study it fell one seven to 154 in combination with Azacitidine.

We expect to file an IND for this trial in the fourth quarter of this year and initiate a phase I E B trial thereafter.

Specific details on the trial design will be forthcoming.

As a class C. D 47 inhibitors have demonstrated clinical activity in both AML and higher risk Mds.

C N opportunity so instead of one seven to one five pool to differentiate from other compounds in the field.

Combined effects of CD 47, blockade and CD 40 co stimulation.

Arundathy Nirmalini Pandite: And today we are excited to announce that we plan to expand into clinical studies in both acute myeloid leukemia and higher risk myeloplastic syndrome. In AML, we plan to study SL172154 in combination with ASO cytotene and Veneto-Klax. In TP-53 mutant AML, as well as in higher-risk MDS, we plan to study cell 172154 in combination with ASA cytidine. We expect to file an IND for this trial in the fourth quarter of this year and initiate a phase 1A, B, trial thereafter. Specific details on the trial design and results will be forthcoming.

Now I would like to turn our attention to 27925 to <unk>.

PD, one FC Ox 40 ligand bifunctional fusion protein.

As most of you know we are currently enrolling in a phase one multi center open label trial to evaluate <unk>. Two 790.252 administered intravenously as monotherapy in patients with advanced solid tumors and lymphoma.

To date, we have enrolled a heavily pre treated predominantly PD one PD one experienced patients population across the initially planned dose escalation cohorts beginning from a first dose level of 10 to the minus four milligrams per kilogram, two six milligrams per kilogram and evaluate that.

Arundathy Nirmalini Pandite: As a class, CD-47 inhibitors have demonstrated clinical activity in both AML and higher-risk MDS. We see an opportunity for SL172154 to differentiate from other compounds in the field due to the combined effects of CD-47 blockade and CD40 co-stimulation. Now I would like to turn our attention to SL 279252, our PD1-FC-ox40 ligand bi-functional fusion proteins.

Two dosing schedule as well.

We have not observed any dose limiting toxicities to the highest dose level.

We have observed dose dependent ox 40 receptor engagement of ups.

<unk> expressing T cells and a primary pharmacodynamic effect showing rapid egress of these targets says from the circulation, which has not previously been reported prior ox 40 agonist antibodies.

Because the emerging data indicate that additional dose levels.

Enable a more complete assessment of PK PD and antitumor activity, we plan to continue to dose escalate through two additional dose levels of 20 milligrams per kilogram and 24 milligrams per kilogram.

Arundathy Nirmalini Pandite: As most of you know, we are currently enrolling in a phase one multi-center open-label trial to evaluate SL279252, administered intravenously as monotherapy in patients with advanced solid tumors and lymphoma. To date, we have enrolled a heavily pre-treated, predominantly CD1, CDL1 experienced patient population across the initially planned dose escalation cohort beginning from our first dose level of 10 to the minus 4 milligrams per kilogram through 6 milligrams per kilogram and evaluated two dosing schedules.

At this time, however, it remains unclear, but ox 40 activation may increase response rates beyond what is expected of PD one inhibition in PD one experienced patients.

Very few patients enrolled to date been known to have PDL, one positive tumors.

Plant now select for patients with known PDL, one positive tumors and we'll be looking for clinical response rates that indicate a possible development path in PD one experienced population.

Arundathy Nirmalini Pandite: We have not observed any dose-limiting toxicities through the highest dose level. However, we have observed dose-dependent ox-40 receptor engagement of ox40 expressing T cells and a primary pharmacodynamic effect showing rapid egress of these target cells from the circulation, which has not previously been reported for prior ox40 agonist antibodies. Because the emerging data indicates that additional dose levels could enable a more complete assessment of PKPD and antitumor activity, we plan to continue to dose escalate through two additional dose levels of 12 milligrams per kilogram and 24 milligrams per kilogram.

As we look forward to the additional data from the higher dose cohort.

Overall, we are pleased with the progress that we have made to date on both of our clinical stage product candidate.

And look forward to the future growth in our clinical development efforts.

Believed that the Pharmacodynamic profile observed at volt.

One seven to 154 and <unk>, two 792, 5% to demonstrate activation of CD <unk> and ox 40, respectively in a manner not seen with prior <unk> and ox 40 agonist antibodies.

This is consistent with the underlying hypothesis.

From which the off platform is derived with that I will now turn the call over to Andrew Our Chief Financial Officer Andrew.

Arundathy Nirmalini Pandite: At this time, however, it remains unclear whether the Oxford deactivation may increase response rates beyond what is expected of PDL1 inhibition in PD1 experienced patients. Because very few patients enrolled to date were known to have PDL1 positive tumors, we plan to now select for patients with known PDL1 positive tumors, and we'll be looking for clinical response rates that indicate a feasible development path in the PD1 experienced population. Thus, we look forward to additional data from the higher dose cohort.

Thank you Lenny and good afternoon, everyone.

As Conor mentioned the full financial results for the second quarter of 2021 are available in our earnings press release, and our forthcoming 10-Q.

Today, I would like to focus on a few key points from our disclosures.

We are fortunate to be well positioned financially.

As of June 32021, we have cash and cash equivalents and short term investments of approximately $304.8 million.

Revenue for the second quarter ended June 32021 was negative $4.2 million compared.

Compared to $3.2 million for the second quarter ended June 32020.

All revenue to date has generated solely from our collaboration agreement with Takeda the negative revenue for the second quarter of 2021 was driven by increased expected costs required to complete our performance obligations in the collaboration agreement as a result of the modifications to our clinical development plan for <unk> 279 two.

Arundathy Nirmalini Pandite: Overall, we are pleased with the progress that we have made to date on both of our clinical stage ARC product candidates and look forward to the future growth of our clinical development efforts. We believe that the pharmacodynamic profiles observed with both SL172154 and SL279252 demonstrate activation of CD40 and Ox 40, respectively, in a manner not seen with cry CD-40 and Ox 40 agonist antibodies.

Two.

The negative revenue does not affect our cash position.

In the second quarter of 2021, our research and development expenses were $14.9 million compared to $7.8 million for the second quarter of 2020.

In the second quarter of 2021, our general and administrative expenses were $5.4 million compared to $1 seven for the second quarter of 2020.

Our net loss for the second quarter of 2021 was $23.6 million or a loss of <unk> 56 per basic and diluted share compared to a net loss of $6.2 million for the second quarter of 2020, or <unk> 81 per basic and diluted share.

Arundathy Nirmalini Pandite: This is consistent with our underlying hypothesis from which the ARC platform is derived. With that, I will now turn the call over to Andrew Neal, our chief financial officer, and

Andrew R. Neill: Thank you, Lenny. And good afternoon, everyone.

Now turning to our financial guidance for 2021 and beyond.

Andrew R. Neill: As Connor mentioned, the full financial results for the second quarter of 2021 are available in our earnings press release and our forthcoming 10Q. Today, I would like to focus on a few key points from our disclosures. We are fortunate to be well positioned financially.

Our financial guidance remains unchanged from the guidance given in connection with our initial public offering in October 2020.

Importantly, the expansion of <unk> 107 to 154 into clinical trials in patients with AML and higher risk Mds does not change our current cash runway guidance because the operating expenses associated with these trials were included in our internal forecasts.

Based on our current and planned operations our expected cash runway remains through year end 2024.

Andrew R. Neill: As of June 30, 2021, we have cash and cash equivalents and short-term investments of approximately $304.8 million. Revenue for the second quarter ended June 30, 2021 was $4.2 million, compared to $3.2 million for the second quarter ended June 30, 2020. All revenue to date is generated solely from our collaboration agreement with Decatur. The negative revenue for the second quarter of 2021 was driven by increased expected costs required to complete our performance obligations under the collaboration agreement as a result of the modifications to our clinical development plan for SL 279-252.

And with that I will now turn the call back over to Taylor Taylor.

Thank you Andrew.

Over the past year Shattuck has made tremendous progress and we are learning how to best apply the arc platform for the benefit of patients with advanced cancers with the learnings from our first two clinical trials.

That's all 107 to $1 four NFL two 795, two have been very well tolerated in humans to date, which bodes well for the arc platform as a whole.

In addition, we have observed an escalating linear relationship between the dose of <unk> administered and the corresponding pharmacodynamic responses to 107 to one four and $2.790 252.

We believe these observations validate one of the central hypothesis to the arc platform that Hex America compounds like Archs will engage TNF receptors in a fundamentally different manner than monoclonal <unk> antibodies.

Our progress with $2.79 to five two has been exciting and we believe that the data collected from additional dose escalation cohorts will allow us to fully characterize the pharmacokinetic profile and to identify the dose at which the pharmacodynamic effects of ox 40 stimulation reach maximum levels.

We began this study in a PDL, one unselected and highly heterogeneous patient population in order to proceed quickly through dose escalation.

Andrew R. Neill: The negative revenue does not affect our cash position. For the second quarter of 2021, our research and development expenses were $14.9 million compared to $7.8 million for the second quarter of 2020. In the second quarter of 2021, our general and administrative expenses were $5.4 million, compared to $1.7 million for the second quarter of 2020. Our net loss for the second quarter of 2021 was $23.6 million, or a loss of 56 cents per basic and diluted share, compared to a net loss of 6.2 million for the second quarter of 2020, or 81 cents per basic and diluted share.

Now that we are within an immunologically active dose range. It is now appropriate to enrich for patients with PD lone positive tumors.

It is not yet clear however, weather ox 40 stimulation will increase response rates beyond what is expected of a PD, one inhibitor and a PD one or PDL, one antibody experienced patient population and the path forward for $2.790, 252 will depend upon observing monotherapy activity.

<unk> in PD, one or PDL, one antibody refractory patients at these higher dose levels.

And enormous opportunity remains to address the unmet need in PD, one and PD lone experienced patients and we are excited to further characterize two 790.252 at higher dose levels in a PD L. One selected patient population.

We are also highly encouraged by the early data from the dose escalation portion of our clinical trial with 107 to 154 in ovarian cancer and look forward to filing our IND for a phase <unk> clinical trial in AML and high risk Mds in the fourth quarter of this year.

Several patients have cleared the dose limiting toxicity window at a dose of three milligrams per kilogram, which is the dose 10 fold higher than the maximum tolerated dose for prior <unk> <unk> agonist antibody therapies.

Andrew R. Neill: Now, turning to our financial guidance for 2021 and beyond. Our financial guidance remains unchanged from the guidance given in connection with our initial public offering in October 2020. Importantly, expanding SL172-154 into clinical trials in patients with AML and higher-risk MDS does not change our current cash runway guidance because the operating expenses associated with these trials were included in our internal forecast. Based on our current and planned operations, our expected cash runway remains through year-end 2024. And with that, I will now turn the call back over to Taylor. Okay?

This is also a dose range at which other CD 47 inhibitors began to achieve high levels of receptor occupancy on CD 47, suggesting that 107 to $1 four may bridge, the perceived GAAP and effectively dosing a CD 40 agonists to the level required for a CD 47 inhibitor.

We believe that expansion into hematologic malignancies with 107 to 154 will further demonstrate one seven to 154 is best in class potential as a CD 47 inhibitor.

The emerging clinical data from one seven to 105, four and $2.795 to suggest that the arc platform has unlocked the TNF superfamily of co stimulatory receptors in a manner that has evaded IGT antibody based modalities for over 20 years.

The data suggests that CD 40 is a very powerful stimulator of the innate immune system.

Taylor H. Schreiber: Thank you, Andrew. Over the past year, Shattuck has made tremendous progress, and we are learning how to best apply the ARC platform for the benefit of patients with advanced cancers based on the learnings from our first two clinical trials. SL172154 and SL279252 have been very well tolerated in humans to date, which bodes well for the ARC platform as a whole. In addition, we have observed an escalating linear relationship between the dose of ARC administered and the corresponding pharmacodynamic responses to 172154 and 279252.

As the effects of ox 40 stimulation are more subtle.

That said, our complete exploration of CD 40, and ox 40, biology has not been possible with Iga antibodies, because escalation to higher dose levels was limited by a combination of toxicity and diminishing signs of immune activation.

We believe the opportunity to compare and contrast, the biologic consequences of CD 40 versus ox 40 activation in just a few months time, we will challenge some of the dogma that has surrounded these targets for decades.

Before we turn to Q&A I would like to close by thanking all of our clinical investigators and their teams and institutions and most importantly, the patients and their families who have participated in our clinical trials and have helped to make this progress possible.

From all of the employees at <unk>, we look forward to the second half of this year and the milestones it will bring.

Taylor H. Schreiber: We believe these observations validate one of the central hypotheses of the ARC platform that hexameric compounds like ARCs will engage TNF receptors in a fundamentally different manner than monoclonal IgG antibodies. Our progress with 279252 has been exciting, and we believe that data collected from additional dose escalation cohorts will allow us to fully characterize the pharmacokinetic profile and to identify the dose at which the pharmacodynamic effects of Ox40 stimulation reach maximum levels.

We appreciate your continued interest in <unk> and look forward to keeping you appraised of our progress throughout the year.

With that operator, I would like to open the call for questions.

Yeah.

At this time to ask a question. Please press star one on your telephone.

To withdraw your question press the pound key.

Please turn borrower, we compile the Q&A roster.

Our first question comes from the line of Mike <unk> from Cowen you may begin.

Alright, Thank you for the human qualities as Ernie Rodriguez for Marc Congratulations on all your progress.

We just have a question a follow up on your commentary regarding the receptor occupancy for the CD 47, Oh I'm sorry.

What was it before.

Have you disclosed what level of receptor occupancy you have you have achieved.

Hum.

Taylor H. Schreiber: We began this study in a PDL1 unselected and highly heterogeneous patient population in order to proceed quickly through dose escalation. Now that we are within an immunologically active dose range, it is now appropriate to enrich for patients with PDL1 positive tumors. It is not yet clear, however, whether Ox 40 stimulation will increase response rates beyond what is expected of a PD1 inhibitor in a PD1 or PDL1 antibody experienced patient population, and the path forward for 279252 will depend upon observing monotherapy activity in PD1 or PDL1 antibody refractory patients at these higher dose levels.

That's helpful.

Others have had.

In order to students.

Oh sure.

Sure hiring and thank you for the question. This is Taylor.

We will be disclosing the specific receptor occupancy levels at <unk>.

However, I can put it.

Most levels into a little bit more context, with what has been reported with some of the other CD 47 targeted agents.

And with.

An antibody like <unk> for example.

That antibody began to see early receptor occupancy on CD 47 Express red blood cells.

And then saw saturation of CD 37 expressing leukocytes.

But that didn't occur until they reached dose levels of roughly 20 milligrams per kilogram.

In contrast, some of the surf Alpha FC fusion proteins.

Have been shown to achieve.

Taylor H. Schreiber: An enormous opportunity remains to address the unmet need in PD1 and PDL1 experience patients, and we are excited to further characterize 279252 at higher dose levels in a PDL1 selected patient population. We are also highly encouraged by the early data from the dose escalation portion of our clinical trial with 172154 in ovarian cancer and look forward to filing our I&D for our Phase 1A, 1B, clinical trial and AML and high-risk MDS in the fourth quarter of this year.

Full occupancy.

With different FC fusion proteins full occupancy can mean different things.

At levels of between one and three milligrams per kilogram.

Our impression of.

The reason why.

Some of the surf Alpha fusion proteins have not.

Reported.

100% occupancy on that.

<unk> 47 positive leukocytes is is not that.

You cannot achieve 100% occupancy on leukocytes that some of the lower affinity or lower avidity.

<unk> FC fusion proteins have a faster off rate.

And fall off CD 47 on leukocytes faster than either high avidity or high affinity Serb alpha fusion protein.

Taylor H. Schreiber: Several patients cleared the dose-limiting toxicity window at a dose of 3 milligrams per kilogram, which is tenfold higher than the maximum tolerated dose for prior CD40 agonist antibodies. This is also a dose range at which other CD-47 inhibitors began to achieve high levels of receptor occupancy on CD-47, suggesting that 172154 may bridge the perceived gap in effectively dosing a CD-40 agonist to the level required for a We believe that expanding into hematologic malignancies with 172154 will further demonstrate 172154's best in class potential as a CD-47 inhibitor.

So hopefully that provides a bit of context.

Okay. That's very helpful. Thank you.

Our next question comes from the line Jonathan Miller from Evercore.

You may begin.

Hi, guys. Thanks for taking my question and I believe looking forward.

And can you just make the clinical data.

We look forward to that.

It seems like.

Escalation on one type of course, so far has been very supportive on safety I should say Christmas.

But no responses yet so now as we're entering the immunologically active dose range what are the biochemical signals, we're going to get it Sidney that that'll get us comfortable with activity.

Given we're sort of just entering that active dose range.

Taylor H. Schreiber: The emerging clinical data from 1721154 and 279252 suggest that the ARC platform has unlocked the TNF superfamily of co-stimulatory receptors in a manner that has evaded IGG antibody-based modalities for over 20 years. The data suggest that CD40 is a very powerful stimulator of the innate immune system, whereas the effects of Ox 40 stimulation are more subtle. That said, a complete exploration of CD40 and OX40 biology has not been possible with IgG antibodies because escalation to higher dose levels was limited by a combination of toxicity and diminishing signs of immune activation. We believe the opportunity to compare and contrast the biologic consequences of CD40 versus OX40 activation in just a few months will challenge some of the dogma that has surrounded these targets for decades.

And then secondly.

As we turn to key indications.

Are you planning to pursue combo trials, obviously, we're starting to mono there.

Competitors have all moved robustly to combo trials until the development do you have any expectations of a meaningful monotherapy activity rate, we're developing in that direction.

Sure. Thank you John I'll take the first part of the question and then <unk>.

The second.

So in terms you can elaborate on my response to the first as well.

What you should expect to see at city with both programs is all of the patient.

<unk> and safety data to date at various dose levels.

The pharmacokinetic profile of the compound across the dose ranges.

And then the Pharmacodynamic effects that will include.

<unk> receptor occupancy.

As Lenny mentioned for the <unk>.

Ox 40, engaging compound 2019 to Margination of ox 40 positive lymphocytes at various dose levels.

Operator: Before we turn to Q&A, I would like to close by thanking all of our clinical investigators, their teams, and institutions, and, most importantly, the patients and their families who have participated in our clinical trials and have helped make this progress possible. From all of the employees at Shattuck, we look forward to the second half of this year and the milestones it will bring. We appreciate your continued interest in Shattuck and look forward to keeping you informed of our progress throughout the year. With that operator, I would like to open the call to questions. At this time, to ask a question, please press star one on your telephone.

And then for both compounds immuno phenotypic data and term cytokine analysis.

As well as antitumor activity.

And.

I will ask Lenny to take the second half of your question there regarding any melanin, yes.

Yeah.

Thank you for the question.

AML Mds monotherapy pushing up this is a very sharp monotherapy.

That's our plan is to go into the combination that quickly.

We are bringing in in an immunologically active dose we're breaching that dose from the phase one ovarian study and our plan is to go quickly into the combinations that I mentioned at the site that they need to flex and with Azacitidine monotherapy.

Operator: This time to ask a question, please press Star 1 on your telephone. And to withdraw your question, press the pound key. Please send by, or we will compile the Kinney roster. Our first question of the Comfort Line is from Mark from Callon. You may begin. Hi, thank you for taking our call. This is Ernie Rodriguez. Congratulations.

It's a type of thing and its entertainment interconnect.

Operator: CD 47 is suprapat on 154. Have you discussed what level of receptor you need?

Yeah.

Okay.

I take it that there is no expectation.

Taylor H. Schreiber: Sure, hi Ernie, and thank you for the question. This is Taylor.

Taylor H. Schreiber: We will be disclosing the specific receptor occupancy levels at SITSE. However, I can put the dose levels into a little bit more context with what has been reported with some of the other CD47 targeted agents. You know, an antibody like Megrolomab, for example. That antibody began to see early receptor occupancy on CD-47 expressing red blood cells and then saw saturation of CD47 expressing leukocytes, but that didn't occur until they reached those levels of roughly 20 milligrams per kilogram.

Manav, it's feeding substantial monotherapy activity, we're developing in that direction.

Yeah.

John.

If you don't mind, John I'll, just make one quick comment on that.

And.

Our guidance around monotherapy antitumor activity for 171.504 is based upon two things.

It's based upon what is known clinically.

About the expected monotherapy activity of the CD 40 agonist as well as what is known clinically about the expected activity of an FC silent SR 47 inhibitor.

And our interpretation of the 20 plus years experience, we have the CD 40 agonist antibodies in human clinical studies.

Taylor H. Schreiber: In contrast, some of the CERF Alpha FEC fusion proteins, have been shown to achieve full occupancy and with different Fc fusion proteins, full occupancy can mean different things, at levels of between one and three milligrams per kilogram. Our impression of the reason why some of the CERP alpha fusion proteins have not reported, 100% occupancy on CD47 positive leukocytes is not that you cannot achieve 100% occupancy on leukocytes, is that some of the lower affinity or lower avidity, serp alpha fc fusion proteins have a faster off rate and fall off CD-47 on leukocytes faster than either high-avidity or high-affinity serp alpha fusion So hopefully that provides a bit of context.

While some agents have shown sporadic monotherapy activity in tumors like melanoma renal cell carcinoma in lymphoma.

There is no consistent pattern of monotherapy activity at least with the CD 40 agonist antibodies.

And because of that we don't feel that its appropriate to frame efficacy expectations around any CD 40 agonists.

Agent.

On the CD 47 side.

The only agents that have shown monotherapy activity.

Those that have residual function in the FC domain.

CD 47, and inventory agents, which lacked that function do not have monotherapy activity and they also don't have talks.

Operator: That's very helpful. Thank you.

And so what that tells you with CDK <unk> inhibitors as a class is that.

Operator: Our next question comes from the line of Jonathan Miller from Evercore. On yesterday, may begin. Hi guys, thanks for taking my question.

<unk> FC domain and the characteristics of the FC domain are in and of themselves sufficient to drive toxicity.

However, what you'll notice about all CD 47 inhibitors, regardless of whether the FC domain is active or inactive is that they are all pursuing registrational pathways in combination either with certain chemotherapies or.

Operator: taking my question, and I'm really looking forward to seeing some of the clinical data at 60. So what do we look forward to that? I mean, it seems like escalation on 1x4 so far has been very supportive of safety, I shouldn't say the very specific details from both programs, but no responses yet. So now as we're entering the immunologically active dose range, what are the biochemical signals we're going to get at Sydney that will make us comfortable with activity given we're sort of just entering that active dose range?

ADP competent tumor targeted antibodies.

So you can that extend the conclusion a bit from there and say that while the FC domain is sufficient for talks and sporadic monotherapy activity, that's insufficient to drive registration.

And so with this agent we are again framing expectations based upon 171 being a CD 47 inhibitor with an inactive FC domain.

Operator: And then secondly, as we turn to heem indications, I think you're planning to pursue combo trials; obviously, we're starting in monotherapies there. Competitors have all moved robustly to combo trials for further development. Do you have any expectations of a meaningful monotherapy activity rate or development in that direction?

Got it great. Thank you.

That's very responsive.

Maybe turning to 252.

Can you speak a little bit to the clinical relevance of absolutely stimulation pushing T cells into the periphery rabbit out of the blood or there are other signs of T cell activation that go along with that.

Granted it's tough to.

Taylor H. Schreiber: Sure, John. I'll take the first part of the question and then ask Lenny to take the second. So in turn, she can elaborate on my response to the first as well. What you should expect to see at SITSE with both programs is all of the patient characteristics and safety data to date at the various dose levels, the pharmacokinetic profile of the compound across the dose ranges, and then the pharmacodynamic effects that will include receptor occupancy, as Lenny mentioned, for the Ox 40 engaging compound 279252, margination of ox40 positive lymph I will ask Lenny to take the second half of your question there regarding AML.

Figure out what's going on given the lack of deal activity in many of these patients but I'm.

I'm trying to focus specifically on ox 40 axis P D and what that can tell us about.

Successful immuno stimulation.

Yeah. Thanks for the question John.

So ox 40, as a as an antigen dependent CD four specific T cell co stimulator.

And so you expect the pharmacodynamic at least the direct pharmacodynamic effects of ox 40 stimulation to be centered on that T cell population and more specifically to.

A subset of the CD four positive box <unk> positive T cells that are actively encountering in this case tumor antigens.

<unk>.

In that subset of cells you.

May I expect those cells to rapidly Kerry.

792 from the peripheral blood into tissues.

Arundathy Nirmalini Pandite: So thank you for the question. With the AMLMBS, the monotherapy portion of this is a very short monotherapy. That's our plan to go into the combination very quickly. So we are bringing in an immunologically active dose. We are bridging that dose from the phase 1 ovarian study, and our plan is to go quickly into the combinations that I mentioned with acesitone, Benetoclax, and with ACE-SIT ad-Mone-Selis, with exercise again, and I am associated with Benito class.

And if that includes tumor tissues, then that could provide a means of actively transporting two 795, two out of the blood and into peripheral tissues, including tumors.

And if those cells are being activated then you would expect to see some signs of that.

That could come in the form of.

Changes to the immuno phenotypic profile of those cells.

Patterns of.

Operator: Okay, sure, so I think that there's no expectation of seeing substantial monotherapy activity there or developing in that direction. On the hip, you're. You don't mind, John.

Activation markers.

Or it could come in other forums, but.

It's hard to say for sure because.

The human experience with ox 40 antibodies.

Contains very very little in the way of convincing pharmacodynamic activity to date.

Taylor H. Schreiber: If you don't mind, John, I'll just make one quick comment on that point. And, you know, our guidance around monotherapy antitumor activity for 172-154 is based on what is known clinically about the expected monotherapy activity of the CD-40 agonist, as well as what is known clinically about the expected activity of an FC silent CD-47 inhibitor. And our interpretation of, you know, the 20 plus years of experience we have had with CD40 agonist antibodies in human clinical studies is that while some agents have shown sporadic monotherapy activity in tumors like melanoma, renal cell carcinoma, and lymphoma, there is no consistent pattern of monotherapy activity, at least with the CD40 agonist antibodies.

And so I think we are.

And in somewhat uncharted territory here for ox 40 agonists.

And therefore.

We want to be sure that we fully explore the.

The dose levels here and identify the dose level at which ox 40 biology at least as far as we can measure it.

Has been maximized.

Great. Thank you very much.

Yeah.

Our next question will come from the line.

Gil Blum from Needham you may begin.

Oh and congrats on all the progress.

It looks like.

Both programs seem to be very big.

But as you dose escalate do you expect at some point to start seeing some level of immune mediated talks job you know.

The sort of low grade rash low grade Crs are seeing sometimes with immuno oncology agents.

Taylor H. Schreiber: And because of that, we don't feel that it's appropriate to frame efficacy expectations around any CD40 agonist agents. On the CD-47 side, the only agents that have shown monotherapy activity are those that have residual function in the epsedome. CD-47 inhibitor agents which lack that function do not have monotherapy activity, and they also don't talk. And so what that tells you about the CD47 inhibitors as a class is that the FC domain and the characteristics of the FC domain are, in and of themselves, sufficient to drive toxicity.

Sure. Thanks for the question I'll ask Lenny to take this one.

Yes, as we dose escalate given that we do have an end to this molecule as well we would expect to see some particularly up talk but we are very encouraged that we are able to dose escalate to the lower doses.

Actually in the CD 40, a tonne.

Target.

For the antibody dose limiting toxicity has precluded dose escalation beyond.

10 milligrams per kilogram that we've been able to dose escalate.

We are currently at three milligrams per kilogram and so it gives us an opportunity to dose escalate to the point that we have.

Taylor H. Schreiber: However, what you notice about all CD-47 inhibitors, regardless of whether the EPC domain is active or inactive, is that they are all pursuing registrational pathways in combination, either with certain chemotherapies or ADCP competent tumor-targeted antibodies. And so you can then extend the conclusion a bit from there and say that while the FC domain is sufficient for talks and sporadic monotherapy activity, it is insufficient to drive registration. And so with this agent, we are again framing expectations based upon 172.

Occupancy unfolds, CD 40, as well as CD 47, and being able to fluctuate those receptors SEC.

In fact encouraged by this dose escalation to be able to do but as you said.

Secondly, I mean, we.

Suddenly monetize patients.

Due to the fact that that could be toxicity at higher doses.

Okay.

And on two sides to just to clarify that.

Stood this correctly. So we're discussing enrichment for patients who are PD one positive.

Operator: Great, thank you. I think that's very responsible.

And PD one refractory following PD one base therapy is that correct.

Operator: Maybe turning to 252, can you speak a little bit to the clinical relevance of Ox40 stimulation pushing T-cells into the periphery out of the blood? Are there other signs of T-thel activation that go along with that? And granted, it's tough to disambiguate what's going on, given the lack of B-L-1's activity in many of these patients. But I'm trying to focus specifically on Ox40 axis PD and, and, and, you know. Thank you.

Yes, that's correct.

That's correct. So the reason for that.

Escalation up to now we did not select.

<unk>.

PDL one positive.

We started at the very low dose and we wanted to get through the dose escalation.

As efficiently as possible to a point that we had an immunologically active dose range and currently we are at that dose range. So moving through but our plan is to select patients with known PDL, one positivity and the reason for that is that one <unk> molecule.

Taylor H. Schreiber: Yeah, thanks for the question, John. So, you know, Ox 40 is an antigen-dependent CD4-specific T-cell co-stimulator. And so you expect the pharmacodynamic, at least the direct pharmacodynamic effects of Ox 40 stimulation to be centered on that T cell population. And more specifically, to a subset of CD4 positive Ox 40 positive T cells that are actively encountering, in this case, tumor antigen. And in that subset of cells, you may expect those cells to rapidly carry 279252 from the peripheral blood into tissues.

<unk> PDL, one and so it would make sense to actually select but that is now we certainly acknowledge that these are patients who have failed <unk>.

181 incentive fees and have either.

Any sense of resistance.

Fluid.

Responding to agents.

Yeah.

Okay that makes that makes a lot of sense.

And maybe a last one on the chip cookies program, which we haven't discussed too much today.

Taylor H. Schreiber: And if that includes tumor tissues, then that could provide a means of actively transporting 279252 out of the blood and into peripheral tissues, including tumors. And if those cells are being activated, then you would expect to see some signs of that. That could come in the form of changes to the immunopinotypic profile of those cells and patterns of activation markers, or it could come in other forms. But it's hard to say for sure because the human experience with ox 40 antibodies has shown very, very little in the way of convincing pharmacodynamic activity to date.

Following kind of the results in this space you know arcas others has there been any additional disclosures regarding whether we're going with it and that's the active or inactive here.

There has not been any additional disclosure, yet, but we will be providing additional guidance around.

Around the next our program to enter the clinic.

Later this year.

Okay excellent.

I'll definitely look forward for your results et cetera. Thank you for taking our questions.

Thanks for the questions.

And our last question will come from the line of the corn shrink from Bamberg you may begin.

Hi, good afternoon, Thanks for taking my question.

So on your first 154 program.

Taylor H. Schreiber: And so I think we are in somewhat uncharted territory here for Ox 40 agonists, and therefore we want to be sure that we fully explore that dose level here and identify a dose level at which Ox40 biology, at least as far as we can measure it, has been maximized.

The the current doses.

Three milligram per kilogram became a Brian Yu the next one.

It seems to be a big jump I guess, what what gives you the.

That level of comfort you can dose escalate too.

Two three times at that kind of goes.

Operator: Great, it makes sense. Thank you very much.

Curious Europe.

Sure. Thanks for the question I'll ask <unk> to take that one as well.

Operator: Our next question will come from the line of Gil Blum from Neatham. You may begin.

Often dose escalate in these oncology studies and have locked in claims.

Operator: And congratulations on all the progress. It looks like the vote programs seem to be very safe. But as you dose escalate, do you expect at some point to start seeing some level of immune-mediated talk of, you know, the sort of low-grade rash, low-grade TRS that we sometimes see sometimes with the immune non-cology agents? Sure, thanks for the question. I'll ask Lenny to take this one.

So that <unk> 10 is a reasonable increase.

Increase that's a half block increase.

And so depending on what we see.

And then we'll determine whether we need to go higher or not but right now that's actually a very reasonably.

Got it and then in terms of next step we use like a recommended phase two dose and.

Moving to the combination.

Oh, that's better.

Arundathy Nirmalini Pandite: Yes, as we dose escalate, given that we do have an agonist and this molecule as well, we would expect to see some degree of top. What we are very encouraged is that we are able to dose escalate through the lower doses, especially in the CD40, targeted with CD40 antibodies, where dose limiting toxicity has precluded dose escalation beyond 0.3 milligrams per kilogram. We've been able to dose escalate, you know; we are currently at 3 milligrams per kilogram, and so it gives us an opportunity to dose escalate to the point where we have receptor occupancy on both CD40 as well.

The combination of phase of the study and guess what.

Any factors you were looking for.

But when you weigh you select the.

It does and where you want to comply with that.

With Rituxan.

Pre tax.

That's in terms of my view of our yard.

Okay.

In the trial.

Sure.

General what we're looking for in identifying a recommended phase II dose.

Is to find a.

A dose which is well tolerated.

There, we see saturation of both targets.

Part of the arc compounds. So in the case of 171 platform that will mean saturation, both C 47, and <unk> 40.

Arundathy Nirmalini Pandite: well as CD 47 and be able to saturate those receptors. So I think we're encouraged by this dose escalation that we're able to do. But as you said, there are certainly, I mean, we certainly monitor our patients with a view to the fact that there could be toxicity at higher doses.

And where we see that.

There has been a continued escalation in the on target Pharmacodynamic effects that we expect to see.

Downstream of that engagement.

Operator: Okay, and on 252, just to clarify that I understood this correctly, so we're discussing enrichment for patients who are

Whereas those pharmacodynamic effects of escalated up to a point and then reached a plateau.

Presumably after you know not every patient will reach maximum pharmacodynamic.

Operator: are PD1 positive and PD1 refractory following PD1-based therapy. Is that correct?

Activation of <unk> 40 at the exact same dose.

Operator: Yes, that's correct. That's right.

And so identification of a maximum plateau may improve the probability there'll be selected dose, which maximizes the biology for all patients we might treat.

Operator: So the reason for that, in our dose escalation up to now, we did not really select for patients who are PDL1 positive. We started at a very low dose, and we wanted to get through the dose escalation as efficiently as possible to a point where we had an immunologically active dose range. And currently, we are at that dose range. So moving forward, our plan is to select patients with no PDL1 positivity. The reason for that is that one end of our molecule binds to PDL1.

Of course, then observation of antitumor activity.

It is important.

And then we should have mentioned this earlier, but also.

And narrowing the dose and schedule.

We will be looking as well as the PK profile and ensuring that not only do we have.

Cheap full occupancy of the targets, but that there is sufficient free drug in the system to maintain full occupancy through the dosing interval.

Operator: And so it would make sense to actually select for that. However, we certainly acknowledge that these are patients who have failed PDL1 therapy and have other mechanisms of resistance that may preclude them from responding to agents such as this.

So collectively those are.

Vectors that we're triangulating to pick a dose going into subsequent studies.

Operator: That makes a lot of sense. And maybe our last one on the Pitchit Pro.

Great. Thanks Tyler.

Sure. Thanks for the question.

Thank you that's all the time, we have for today's Q&A session of the call.

Operator: on the Titch's program, which we haven't discussed too much today. Following kind of the results in the space, you know, Arcus and others, has there been any, you know, additional disclosures regarding whether we're going with an SC active or an SC inactive here? There has not been any additional disclosure yet, but we will be providing additional guidance around the next ARC program to enter the clinic.

This time I would like to turn the call back over to Taylor Schreiber, Chief Executive Officer for closing remarks.

Thank you operator, and thank you all for joining the Schaddick labs second quarter financial results and business update conference call.

We appreciate your continued interest in <unk> and we look forward to updating you on our milestones throughout the remainder of this year. Thanks very much.

Yeah.

Operator: Okay, excellent. And we all definitely look forward to your

This concludes today's conference call. Thank you for participating you may now disconnect have a wonderful day.

Operator: I definitely look forward to your results at Settee. Thank you for taking our questions.

[music].

Operator: And the last question. Confirmine, I know it is the Kwan Shoe from Bamberg.

Operator: You may begin.

Operator: Hi, good afternoon. Thanks for taking my questions. So on your first 154 program, the current dose is three.

Operator: 3 milligrams, the kilogram, the next one is 10. It seems to be a big jump. I guess what gives you that level of comfort is that you can't dose as well as well as well than two, three times that amount of your current dose.

Operator: Sure, hi Zee, thanks for the question. I'll add to me to take that one as well.

Arundathy Nirmalini Pandite: Ziz, we often dose escalate in these oncology studies by half-long increments. So that three to ten is a reasonable increase; that's a half-lock increase. And depending on what we see at 10, then we'll determine whether we need to go higher or not. But right now, that's actually a very reasonable increase.

Operator: Got it. And then, in terms of the next step we select, I recommend

Operator: Step, when you select the recommended phase two dose and go moving to the combination phase of the study, a combination phase of the study, I guess what a gaining factor here we're looking for when you select the dose and when you want to combine with the retuxma. Casamabia, you are a respect, you know.

Operator: Sure. So, in general, what we're looking for in identifying a recommended phase two dose is a dose that is well-tolerated where we see saturation of both targets of the arc compounds. So in the case of 172154, that will mean saturation of both CD-47 and CD40, and where we see that there has been a continued escalation in the on-target pharmacodynamic effects that we expect to see downstream of that engagement, and wherein those pharmacodynamic effects have escalated up to a point and then reached a plateau.

Operator: Presumably, after, you know, not every patient will reach maximum pharmacodynamic activation of CD40 or Ox 40 at the exact same dose. And so identification of a maximum plateau may improve the probability that we select a dose which maximizes the biology for all patients we might treat. Of course, then observation of antitumor activity is important. And then, we should have mentioned this earlier, but also in narrowing the dose and schedule, we'll be looking as well at the PK profile and ensuring that not only do we achieve full occupancy of the targets but that there is sufficient free drug in the system to maintain full occupancy through the dosing interval. So collectively, those are the vectors that we're triangulating to pick a dose going into subsequent studies.

[music].

Operator: Thank you. That's all the time we have for today's three and a half hour session of the call. At this time, I would like to turn the call back over to Taylor Shriver, Chief Executive Officer of Shaddle Gras, for closing remarks. Thank you.

Taylor H. Schreiber: Thank you, Operator, and thank you all for joining the Shattuck Lab's second quarter financial results and business updates conference call. We appreciate your continued interest in Shattuck, and we look forward to updating you on our milestones throughout the remainder of the call. Thank you.

Operator: This includes today's conference call. Thank you for participating. You may now disconnect. Have a wonderful day.

Operator: and so, and and and and and and and and. Thank you, I. Thee and and and and You're and You're, Thank you, and so on the way. Thank you. Thank you, and so much. Thank you. Thank you. Thank you.

Operator: Good afternoon, everyone, and welcome to Shattuck Labs' second quarter financial results and business updates call. Today's call is being recorded at this time. I would like to turn the call over to Connor Richardson, Senior Director of Finance and Investor Relations at Shattuck Labs.

Conor Richardson: Thank you, operator. Good afternoon, everyone, and welcome to the Shattuck Labs Conference Call to discuss our second quarter financial results and business update. The press release for our financial results was issued after market close this afternoon and can be found in the events and presentations section of our website, shaddocklabs.com. During this afternoon's call, the Shattuck team will provide a business overview of the second quarter of 2021, including an update on our clinical development plans for SL 172154 and SL 279252.

Conor Richardson: A Q&A session will follow our prepared remarks. Joining me on the call today are Dr. Taylor Shriver, our chief executive officer; Dr. Lini Pandit, our chief medical officer; Andrew Neal, our chief financial officer; and KC. D. Young, our chief business officer. Before we begin, I would like to remind you that today's webcast contains forward-looking statements, within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements represent management's judgment as of today and may involve certain risks and uncertainties that could cause actual results to differ materially from those expressed in or implied by these statements.

Conor Richardson: For more information on these risks and uncertainties, please refer to our most recent annual report on Form 10K for the year ended December 31st, 2020, and our other filings with the SEC, which are available from the SEC's website or on our corporate website, shot at clabs. Any forward-looking statements represent our views as of today, August 11, 2021. With that, I will now turn the call over to Taylor Shriver, our chief executive officer. Thank you, Connor.

Taylor H. Schreiber: Good afternoon, everyone, and thank you for joining us. Today's earnings call is the first since our initial public offering in October of 2020, and I am exceptionally proud of the milestones our team has achieved since that time. Our clinical team has done an outstanding job of advancing the clinical development of both SL172154 and SL279252, our clinical stage agonist redirected checkpoint or arc compounds. As a reminder, 172154 is a SERP Alpha FCC-D-40 ligand, bi-functional fusion protein currently in two different phase one clinical trials, one for patients with advanced ovarian cancer and another for patients with squamous cell carcinoma Our second clinical stage compound, 279252, a PD1-FC-Ligand bi-functional fusion protein, is being developed in collaboration with Takeda Pharmaceuticals and is in phase one development for patients with advanced solid tumors.

Taylor H. Schreiber: Both of our ARC product candidates are first-in-class compounds that entered the clinic in less than four years since our founding due to the pioneering work of our scientific, manufacturing, and regulatory teams. We are currently generating clinical data to validate the concept behind the ARC platform, and we are particularly excited to share this clinical progress with you in just a few months. Specifically, we have submitted our clinical data from the monotherapy dose escalation portion of our phase one clinical trials for 172154 and 279252 to the Society for Immunotherapy of Cancer, also known as SITC, for presentation at its annual meeting on November 10th through November 12th. Emerging data has guided us to amend and expand our clinical trials, and today we will provide some context for those expansions in addition to our general corporate updates. During 2021, we have made steady progress towards advancing the dose escalation cohorts for 172154 in patients with relapsed or refractory ovarian cancer.

[music].

Thank you operator.

Good afternoon, everyone and welcome to the Shaddock Lab's conference call to discuss our second quarter financial results and business updates. The press release for our financial results was issued after market close this afternoon and can be found on the events and presentations section of our website Shattuck.

Taylor H. Schreiber: We are pleased by the safety and tolerability profile observed thus far and are continuing to dose escalate into the higher dose level cohort. Given the totality of the data to date, we have begun to execute on our strategy to broaden clinical development into hematologic malignancies. Specifically, we will soon initiate a clinical trial for patients with acute myeloid leukemia, including a TP53 mutant acute myeloid leukemia cohort, as well as for patients with higher-risk myeloplastic syndrome.

<unk> Dot com.

During this afternoon's call the shadow team will provide a business overview of the second quarter of 2021.

<unk>, an update to our clinical development plans for S. L 107 to 154 and S. L 279 to five two.

A Q&A session will follow our prepared remarks, joining me on the call today are Dr. Taylor Schreiber, our Chief Executive Officer, Dr. Larry <unk>, Our Chief Medical Officer, Andrew Neil Our Chief Financial Officer, <unk>, <unk>, our Chief business Officer.

Such statements represent managements judgment as of today and may involve certain risks and uncertainties that could cause actual results to differ materially from those expressed in or implied by these statements for more information on these risks and uncertainties. Please refer to our most re.

<unk> annual report on Form 10-K for the year ended December 31st 2020, and our other filings with the SEC, which are available from the SEC's website or on our corporate website Shattuck labs dot com.

Any forward looking statements represent our views as of today August 11th 2021.

Taylor H. Schreiber: Turning to our corporate update, it is my pleasure to introduce Dr. Abanov Shukla, who joined us this quarter as our chief technical officer. Abinop has held both technical and leadership roles at large pharmaceutical companies, contract manufacturing organizations, and small biotechnology companies. He brings a wealth of experience to our growing biologics manufacturing team. Abanov's experience across the full spectrum of biologics manufacturing is a critical advantage as we continue to build our internal capabilities. I am very pleased to welcome Abinov to our executive team.

With that I will now turn the call over to Taylor Schreiber, our Chief Executive Officer Taylor.

Thank you Conor and good afternoon, everyone and thank you for joining us.

Today's earnings call is the first since our initial public offering in October of 2020, and I am exceptionally proud of the milestones our team has achieved since that time.

Our clinical team has done an outstanding job of advancing the clinical development of both sell one seven to 154 and it fell to 795 to our clinical stage agonist re directed checkpoint or arc compounds.

As a reminder, one seven to 154 as a surf Alpha F. C. C. D 40 ligand bifunctional fusion protein currently in two different phase one clinical trials, one for patients with advanced ovarian cancer.

Taylor H. Schreiber: Today's call will discuss select clinical data from our ARC platform, which we plan on unveiling in greater detail at SITSI later this year, as well as insights into our clinical strategy. Lenny will discuss our clinical development programs to date. Then Andrew will provide the financial update for the second quarter of 2021, and then I will be back for some concluding comments. With that, I will now turn the call over to Linnie Pandit, our chief medical officer. Lenny?

And another for patients with squamous cell carcinoma of the head and neck or skin.

We are currently generating clinical data to validate the concept behind the arc platform and we are particularly excited to share. This clinical progress with you in just a few months' time.

Arundathy Nirmalini Pandite: Thank you, Taylor, and good afternoon, everyone. First, I would like to discuss our lead clinical program, SL172154, which is a CERPALFA-CD40 ligand bi-functional fusion protein. As a reminder, SL172154 contains the extracellular domain of the human serp alpha protein, which directly binds to and inhibits CD-47. In addition, SL172154 also contains the extracellular domain of the human CD40 ligand protein to simultaneously and directly activate the CD40 research. As most of you know, we are currently exploring SL172154 in two ongoing phase one clinical trials.

Specifically, we have submitted our clinical data from the monotherapy dose escalation portion of our phase one clinical trials for one seven to $1 four and $2.795 two.

To the society for immunotherapy of cancer also known as <unk> for presentation at its annual meeting on November 10th through 14th.

Emerging data has guided us to amend and expand our clinical trials and today, we will provide some context for those expansions. In addition to our general corporate update.

During 2021, we have made steady progress towards advancing the dose escalation cohorts for one seven to 154 in patients with relapsed or refractory ovarian cancer.

We are pleased by the safety and Tolerability profile observed thus far and are continuing to dose escalate into the higher dose level cohorts.

Given the totality of the data to date, we have begun to execute on our strategy to broaden clinical development into hematologic malignancies.

Arundathy Nirmalini Pandite: Our first clinical study of SL172154 is a multi-center, open-label, dose escalation trial intended to assess the safety, tolerability, pharmacokinetics, antitumor activity, and pharmacodynamic effects of intravenous administration of SL172154 as monotherapy in patients with relapsed, refractory ovarian cancer. Enrollment in the monotherapy dose escalation cohorts has progressed smoothly.

Specifically, we will soon initiate a clinical trial for patients with acute myeloid leukemia, including a T. P 53 mutant acute myeloid leukemia cohort.

As well as for patients with higher risk Myelodysplastic syndrome.

We see an opportunity for 170.154 to potentially emerge as a best in class compound for these patient populations.

We have also made significant progress in our clinical development efforts for $2.790 252.

We have completed enrollment through the six milligram per kilogram dose level evaluated both weekly and biweekly dosing schedules and gained enormous insights regarding the behavior of arc compounds in patients with cancer.

Arundathy Nirmalini Pandite: We are currently completing enrollment at the fourth dose level of 3 milligrams per kilogram, and we plan to proceed to the next dose level of 10 milligrams per kilogram thereafter. Our second clinical trial of SL172154 is an ongoing multi-center, open-label, dose escalation clinical study intended to assess the safety, solorability, pharmacokinetics, tumor activity, and pharmacodynamic effects of intratumoral administration of SL172154 as monotherapy in patients with relapsed refractory squamous cell carcinoma of the hipisive. The head and neck or skin.

Turning to our corporate update it is my pleasure to introduce Dr. <unk> <unk>, who joined US this quarter as our Chief Technical Officer.

<unk> has held both technical and leadership roles at large pharmaceutical companies contract manufacturing organizations and small biotechnology companies. He brings a wealth of experience to our growing biologics manufacturing team.

<unk> experience across the full spectrum of biologics manufacturing is a critical advantage as we continue to build our internal capabilities.

I'm very pleased to welcome <unk> to our executive team.

Today's call will discuss select clinical data from our <unk> platform, which we plan on unveiling in greater detail at <unk> later, this year as well as insights into our clinical strategy.

Lenny will discuss our clinical development programs to date.

Then Andrew will provide the financial update for the second quarter of 2021, and then I'll be back for some concluding comments.

With that I will now turn the call over to Linda <unk>, Our Chief Medical Officer Lenny.

Thank you Taylor and good afternoon, everyone first I would like to discuss our lead clinical program <unk> seven to one fateful, which is a step outside FC CD 40 ligand bifunctional fusion protein.

And to remind that one seven until wildfire four contains the extracellular domain of the human <unk> protein, which directly bind to and inhibit <unk> 47.

Arundathy Nirmalini Pandite: On the CD 47 side, consistent with our preclinical data, we have not observed any evidence of anemia or thrombocytopenia, which we believe is due to the selection of an effective silence FC region for SL172154. We believe this contributes to the safety profile and differentiates the cell 17254 from other CD 47 inhibitors with active FC2-154. domains that have reported anemia or pompositopenia in clinical studies.

In addition, <unk> until one fateful also contains the extracellular domain of the human CD 40 ligand protein this simultaneously and directly activate the CD 40 receptor.

As most of you know we are currently exploring <unk> seven to 154 in two ongoing phase one clinical trials.

Our first clinical study of <unk>, 7% to one five Paul is a multi center open label dose escalation trial intended to assess the safety Tolerability pharmacokinetics antitumor activity and Pharmacodynamic effects.

Arundathy Nirmalini Pandite: On the CD-40 side, it is worth remembering that CD-40 agonist antibodies have been in clinical testing for well over 20 years, but progress has been repeatedly hampered by a combination of toxicities at low doses and evidence of a well-shaped dose response curve. In the case of SL172154, clearing the 3 milligrams per kilogram dose level would be a major milestone because previously studied CD40 agonists encountered dose-limiting toxicities including a combination of cytokine release syndrome and liver dysfunction above doses of roughly 0.3 milligrams per kilogram, which is one-tenth the current dose level of SL1.7 to 1.54.

Intravenous administration of Multistem into wildfire full as monotherapy in patients with relapsed refractory ovarian cancer.

Enrollment in the monotherapy dose escalation cohort has progressed smoothly.

Currently completing enrollment at the fourth dose level of three milligrams per kilogram and we plan to proceed to the next dose level of 10 milligrams per kilogram thereafter.

Our second clinical trial of <unk>, 7% to 154 is an ongoing multi center open label dose escalation clinical study intended to assess the safety Tolerability pharmacokinetics antitumor activity and pharmacodynamic effects of intra Tumoral <unk>.

Arundathy Nirmalini Pandite: To date, we have observed none of these adverse events, yet we have observed unique evidence of CD40 engagement and pharmacodynamic activity. We plan to share further details at the SITC conference later this year. We are very excited and encouraged by the emerging profile of SL 172154 and believe that we have entered an immunologically active therapeutic window not seen with prior CD40 agony. The emerging profile of SL 17254 has prompted us to initiate our plans to bridge an immunologically active dose from the Phase 1A clinical trial in ovarian cancer to the Phase 1A, 1B clinical trial in hematologic malignancy.

Ministration of one 7% to one five as monotherapy in patients with relapsed refractory squamous cell carcinoma of the head and neck or skin.

We remain on track to present initial data from this study in the first half of 2022.

Overall, we are very pleased with the emerging profile of <unk>, one seven to one faithful to date no dose limiting toxicities have been upset and either clinical trial and we are encouraged by our ability to dose in the higher dose level cohorts.

Arundathy Nirmalini Pandite: And today we are excited to announce that we plan to expand into clinical studies in both acute myeloid leukemia and higher risk myeloplastic syndrome. In AML, we plan to study SL172154 in combination with ASO cytotene and Bonito-Clac. In TP 53 mutant AML, as well as in higher-risk MDS, we plan to study cell 172154 in combination with ASA cytidine. We expect to file an IND for this trial in the fourth quarter of this year and initiate a phase 1A, B trial thereafter. Specific details on the trial design and results will be forthcoming.

Because the S. L. One 7% to one five pool contains both CD 47 inhibitor and CD four T agonist domains. This safety data should be considered in the context with Tri Ed CD 47, inhibited and safety 40 agonists.

On the C. D 47 side consistent with our preclinical data we have not observed any evidence of anemia or thrombocytopenia, which we believe is due to the selection of an effective silent FC region for <unk> seven to one platform. We believe this.

Contribute to the safety profile and differentiate itself one seven to 154 from other CD 47 inhibitors with active FC domains that have reported anemia or thrombocytopenia in clinical studies.

On the C. D 40 side. It is worth remembering that <unk> agonist antibodies have been in clinical testing for well over 20 years, but progress has been repeatedly has led by a combination of toxicities at low doses and evidence of a bell shaped Bill Smith.

Cub.

In the case of <unk> was 71 five for planning the three milligram per kilogram dose level would be a major milestone because previously studied CD 40, <unk> agonist and content dose limiting toxicities, including a combination of cytokine release syndrome and liver dysfunction.

Arundathy Nirmalini Pandite: As most of you know, we are currently enrolling in a phase one multi-center open-label trial to evaluate cell 279252, administered intravenously as monotherapy in patients with advanced solid tumors and lymphoma. To date, we have enrolled a heavily pre-treated, predominantly PD1, CDL1 experienced patient population across the initially planned dose escalation cohorts, beginning from our first dose level of 10 to the minus 4 milligrams per kilogram through 6 milligrams per kilogram, and evaluated two dosing schedules. We have not observed any dose-limiting toxicities at the highest dose level.

<unk> above doses of roughly 0.3 milligrams per kilogram, which is 110th the current dose level of <unk> seven to one fateful.

To date, we have upset that none of these adverse events and we have observed unique evidence of CD 40 engagement and pharmacodynamic activity.

We plan to share the details at the Citi Conference later this year.

We are very excited and encouraged by the emerging profile of.

<unk> added one 7% to 154 and believe that we have entered an immunologically active therapeutic window not seen with prior CD 40 agonists.

Arundathy Nirmalini Pandite: We have observed dose-dependent ox-40 receptor engagement of ox40 expressing T cells and a primary pharmacodynamic effect showing rapid egress of these target cells from the circulation, which has not previously been reported for prior ox40 agonist antibodies. Because the emerging data indicates that additional dose levels could enable a more complete assessment of PKPD and antitumor activity, we plan to continue to dose escalate through two additional dose levels of 12 milligrams per kilogram and 24 milligrams per kilogram.

The emerging profile of <unk>, one seven to one pipeful has prompted us to initiate our planned to bridge an immunologically active dose from the phase one eight clinical trial in ovarian cancer to the phase one <unk>, one <unk> clinical trial in hematologic malignancies.

And to date, we are excited to announce that we plan to expand into clinical studies in both.

Acute myeloid leukemia and high risk Myelodysplastic syndrome.

In an email we plan to study <unk> 171 faithful in combination with Azacitidine and Lenny to flex in DP 50, <unk> mutant AML as.

As well as in higher risk Mds, we plan to study <unk>, one seven to 154 in combination with Azacitidine.

We expect to file an IND for this trial in the fourth quarter of this year and initiate a phase one b trial thereafter.

Specific details on the trial design will be forthcoming.

As a class C. D 47 inhibitors have demonstrated clinical activity in both AML and higher risk Mds.

They see an opportunity for seven months seven to one five pool to differentiate from other compounds in the field due to the combined effects of CD 47 blockade and CD 40 co stimulation.

Now I would like to turn our attention to <unk>.

279 to five two.

Our PD one FC Ox 40 ligand bifunctional fusion protein as.

As most of you know we are currently enrolling in a phase one multi center open label trial to evaluate itself to 790.252 administered intravenously as monotherapy in patients with advanced solid tumors and lymphoma.

Andrew R. Neill: This is consistent with our underlying hypothesis from which the ARC platform is derived. With that, I will now turn the call over to Andrew Neal, our chief financial officer.

Andrew R. Neill: Thank you, Lenny. And good afternoon, everyone.

To date, we have enrolled a heavily pre treated pay dominantly PD one PDL one experienced patient population across the initially planned dose escalation cohorts beginning from a first dose level of 10 to the minus four milligrams per kilogram, two six milligrams per kilogram and evaluated.

Two dosing schedules.

We have not observed any dose limiting toxicities to the highest dose level.

We have observed dose dependent ox 40 receptor engagement of spotty expressing T cells.

And our primary Pharmacodynamic effect, showing rapid egress of these target cells from the circulation, which has not previously been reported the prior ox 40 agonist antibodies.

Because the emerging data indicate that additional dose levels could enable a more complete assessment of PK PD and antitumor activity. We plan to continue to dose escalate to dose two additional dose levels of 12 milligrams per kilogram and 24 milligrams per kilogram.

Ed.

At this time however, it remains unclear with ox 40 activation may increase response rates beyond what is expected of PD one inhibition in PD one experienced patients.

Because very few patients enrolled to date been known to have PDL, one positive until months, we plan to now select for patients with known PDL, one positive tumors and we'll be looking for clinical response rates that indicate a possible development path in PD One X P.

<unk> population.

So as we look forward to the additional data from the higher dose cohorts.

Overall, we are pleased with the progress that we have made to date on both of our clinical stage product candidate and look forward to the future growth in our clinical development efforts.

We believe that the pharmacodynamic profile observed at volt.

One seven to 154 and <unk>, two 792, 5% to demonstrate activation of CD <unk> and ox 40, respectively in a manner not seen with prior CD 40 in Oxford the agonist antibodies.

This is consistent with our underlying hypothesis.

From which the off platform is derived with that I will now turn the call over to <unk>, Our Chief Financial Officer Andrew.

Andrew R. Neill: Now, turning to our financial guidance for 2021 and beyond, our financial guidance remains unchanged from the guidance given in connection with our initial public offering in October 2020. Importantly, expanding SL172-154 into clinical trials in patients with AML and higher-risk MDS does not change our current cash runway guidance because the operating expenses associated with these trials are included in our internal forecast. Based on our current and planned operations, our expected cash runway remains through year-end 2024. And with that, I will now turn the call back over to Taylor. Taylor?

Thank you Lenny and good afternoon, everyone.

As Conor mentioned the full financial results for the second quarter of 2021 are available in our earnings press release, and our forthcoming 10-Q.

Today, I would like to focus on a few key points from our disclosures.

We are fortunate to be well positioned financially.

As of June 32021, we have cash and cash equivalents and short term investments of approximately $304.8 million.

Revenue for the second quarter ended June 32021 was negative $4.2 million compared.

Compared to $3.2 million for the second quarter ended June 32020.

<unk>.

The negative revenue does not affect our cash position.

In the second quarter of 2021, our research and development expenses were $14.9 million compared to $7.8 million for the second quarter of 2020.

In the second quarter of 2021, our general and administrative expenses were $5.4 million compared.

Compared to $1 seven for the second quarter of 2020.

Now turning to our financial guidance for 2021 and beyond.

Our financial guidance remains unchanged from the guidance given in connection with our initial public offering in October 2020.

Based on our current and planned operations our expected cash runway remains through year end 2024.

And with that I will now turn the call back over to Taylor Taylor.

Thank you Andrew.

Over the past year Shattuck has made tremendous progress and we are learning how to best apply the arc platform for the benefit of patients with advanced cancers, but the learnings from our first two clinical trials.

That's all 107 to $1 four NFL two 795, two have been very well tolerated in humans to date, which bodes well for the arc platform as a whole.

In addition, we have observed an escalating linear relationship between the dose of <unk> administered and the corresponding pharmacodynamic responses to 171, four and $2.790 252.

We began this study in a PDL, one unselected and highly heterogeneous patient population in order to proceed quickly through dose escalation.

Taylor H. Schreiber: An enormous opportunity remains to address the unmet need in PD1 and PDL1 experience patients, and we are excited to further characterize 279252 at higher dose levels in a PDL1 selected patient population. We are also highly encouraged by the early data from the dose escalation portion of our clinical trial with 172154 in ovarian cancer and look forward to filing our I&D for our Phase 1A, 1B, clinical trial in AML and high-risk MDS in the fourth quarter of this year.

Now that we are within an immunologically active dose range. It is now appropriate to enrich for patients with PD lone positive tumors.

It is not yet clear however, weather ox 40 stimulation will increase response rates beyond what is expected of a PD, one inhibitor and a PD one or PDL, one antibody experienced patient population and the path forward for $2.795, two will depend upon observing monotherapy activity.

<unk> in PD, one or PDL, one antibody refractory patients at these higher dose levels.

Taylor H. Schreiber: Several patients cleared the dose-limiting toxicity window at a dose of 3 milligrams per kilogram, which is tenfold higher than the maximum-tolerable dose for prior CD-40 agonist antibodies. This is also a dose range at which other CD-47 inhibitors began to achieve high levels of receptor occupancy on CD-47, suggesting that 172154 may bridge the perceived gap in effectively dosing a CD-40 agonist to the level required for We believe that expanding into hematologic malignancies with 172154 will further demonstrate 172154's best in class potential as a CD-47 inhibitor.

And enormous opportunity remains to address the unmet need in PD, one and PDL one experienced patients and we are excited to further characterize two 790.252 at higher dose levels in a PD L. One selected patient population.

This is also a dose range at which other CD 47 inhibitors began to achieve high levels of receptor occupancy on CD 47, suggesting that 107 to 154 May bridge, the perceived GAAP and effectively dosing a CD 40 agonists to the level required for a CD 47 inhibitor.

Taylor H. Schreiber: The emerging clinical data from 1721154 and 279252 suggest that the ARC platform has unlocked the TNF superfamily of co-stimulatory receptors in a manner that has evaded IGG antibody-based modalities for over 20 years. The data suggest that CD40 is a very powerful stimulator of the innate immune system, whereas the effects of Ox 40 stimulation are more subtle. That said, a complete exploration of CD40 and Ox 40 biology has not been possible with IgG antibodies because escalation to higher dose levels was limited by a combination of toxicity and diminishing signs of immune activation. We believe the opportunity to compare and contrast the biological consequences of CD40 versus Ox 40 activation in just a few months' time will challenge some of the dogma that has surrounded these targets for decades.

We believe that expansion into hematologic malignancies with 170.154 will further demonstrate one seven to $1 four is best in class potential as a CD 47 inhibitor.

The emerging clinical data from 170, 154, and $2.795 to suggest that the arc platform has unlocked the TNF superfamily of co stimulatory receptors in a manner that has evaded IGT antibody based modalities for over 20 years.

The data suggests that <unk> 40 is a very powerful stimulator of the innate immune system.

As the effects of ox 40 stimulation are more subtle.

From all of the employees at <unk>, we look forward to the second half of this year and the milestones it will bring.

We appreciate your continued interest in <unk> and look forward to keeping you appraised of our progress throughout the year.

With that operator, I would like to open the call for questions.

Operator: This time to ask a question, please press Star 1 on your telephone. And to withdraw your question, press the pound key.

This time to ask a question. Please press star one on your telephone and toured draw your question press the pound key.

Operator: Please sign by where we compile the Kinney roster. Our first question is from Mark from Comfort Line on Mark from Callan. You may begin. Hi, thank you for taking our call. This is Ernie Rodriguez for a month.

Please turn borrower, we compile the Q&A roster.

Our first question will come from the line of Mike from from Cowen You May begin.

Alright, Thank you for <unk>.

Operator: Hi, thank you for taking our call. This is Ernie Rodriguez for Marks. Congratulations on all your progress. We just have a question, follow up on your

Rodriguez for remarks, congratulations on your progress.

We just have a question a follow up on your commentary regarding the receptor occupancy for the CD 47, Oh I'm sorry.

Operator: CD 47 Surpa and 154. Have you discussed what level of receptor of co-keepingcy you have?

Unwanted support.

Have you disclosed what level of receptor occupancy.

We have achieved.

And if this level is above what others have seen or experienced in Europe.

Taylor H. Schreiber: Sure. Hi Ernie. Thank you for the question. This is Taylor.

Thanks.

Sure Hi, Eric and thank you for the question. This is Taylor.

Taylor H. Schreiber: We will be disclosing the specific receptor occupancy levels at SITSE. However, I can put the dose levels into a little bit more context with what has been reported with some of the other CD47 targeted agents. You know, an antibody like Megrolomab, for example. That antibody began to see early receptor occupancy on CD47-expressing red blood cells and then saw saturation of CD47-expressing leukocytes, but that didn't occur until they reached those levels of roughly 20 milligrams per kilogram.

We will be disclosing the specific receptor occupancy levels at cincy.

However, I can put.

The dose levels into a little bit more context, with what has been reported with some of the other CD 47 targeted agents.

And with that.

An antibody like <unk> for example.

That antibody began to see early receptor occupancy on CD, 47 express and Red blood cells.

And then saw saturation of CD 47 expressing leukocytes.

But that didn't occur until they reached dose levels of roughly 20 milligrams per kilogram.

Taylor H. Schreiber: In contrast, some of the CERF Alpha FEC fusion protein, have been shown to achieve full occupancy, and with different F.Pusion proteins, full occupancy can mean different things, at levels of between one and three milligrams per kilogram. Our impression of the reason why some of the CERP alpha fusion proteins have not reported, 100% occupancy on CD47 positive leukocytes is not that you cannot achieve 100% occupancy on leukocytes, is that some of the lower affinity or lower avidity, serf alpha fc fusion proteins have a faster off rate and fall off CD47 on leukocytes faster than either high-abidity or high affinity serp alpha fusion So hopefully that provides a bit of context.

In contrast to some of the <unk> Alpha FC fusion proteins.

<unk> shown to achieve full.

Full occupancy.

With different FC fusion proteins full occupancy can mean different things.

At levels of between one and three milligrams per kilogram.

Our impression of.

The reason why some of the surf Alpha fusion proteins have not.

Reported.

100% occupancy on CD 47 positive leukocytes is is not that.

You cannot achieve 100% occupancy on leukocytes that some of the lower affinity or lower avidity.

<unk> FC fusion proteins have a faster off rate.

And fall off CD 47 on leukocytes faster than either high avidity or high affinity Serb alpha fusion proteins.

Operator: Yeah, that's very helpful. Thank you.

So hopefully that provides a bit of context.

Operator: Our next question comes from the line of Jonathan Miller from Evercore on the S&A. May begin.

Okay. That's very helpful. Thank you.

Our next question comes from the line of Jonathan Miller from Evercore.

Operator: Hi guys, thanks for taking my question and I'm really looking forward to seeing some of the same ethnic data at the 50s. So what do we look forward to that? I mean, it seems like escalation on 1 54 so far has been very supportive of safety, I shouldn't say the basis for both programs, but no responses yet. So now, as we're going to be very supportive of safety,

May begin.

Oh, Hey, guys. Thanks for taking my question and I'm really looking forward to seeing clinical data.

We look forward to that.

It is like.

Escalation on 154, so far has been very supportive on safety I should say the Christmas broker guidance, but no responses yet so now as we're entering the immunologically active dose range one of the biochemical signals, we're going to get it Sidney that that'll get us comfortable with activity.

Operator: We're entering the immunologically active dose strain

Operator: What are the biochemical signals we're going to get at Sydney that will get us comfortable with activity given we're sort of just entering that active dose range? And then, secondly, as we turn to heem indications, I see that you're planning to

Given we're sort of just entering that active dose range.

And then secondly.

As we turn to key indications.

Operator: Combination trials, obviously starting mono there, competitors have all moved robustly to combo trials for further development. Do you have any expectations of a meaningful monotherapy activity rate or development in that direction?

Planning to pursue combo trials I'm going to start a mono there.

Competitors have all moved robustly to combo trials until the development do you have any expectations of a meaningful monotherapy activity rate or development in that direction.

Taylor H. Schreiber: Sure, thank you, John. I'll take the first part of the question and then ask Lenny to take the second. So in turn, she can elaborate on my response to the first as well. What you should expect to see at SITSE with both programs is all of the patient characteristics and safety data to date at the various dose levels, the pharmacokinetic profile of the compound across the dose range, and then the pharmacodynamic effects that will include receptor occupancy, as Lenny mentioned for the Ox40 engaging compound 279252, margination of ox40 positive lymphocytes I will ask Lenny to take the second half of your question there regarding AML.

Sure. Thank you John I'll take the first part of the question and then ask Lenny to take the second.

So in insurance you can elaborate on my response to the first as well.

What you should expect to see that city with both programs is all of the patient.

Patient characteristics and safety data to date at various dose levels.

The pharmacokinetic profile of the compound across the dose ranges.

And then the Pharmacodynamic effects that will include.

Receptor occupancy.

As Lenny mentioned for the <unk>.

Ox 40, engaging compound to $702 five to Margination of ox 40 positive lymphocytes at various dose levels.

And then for both compounds immuno phenotypic data in term cytokine analysis.

As well as antitumor activity.

And.

I will ask Lenny to take the second half of your question there regarding AML and Mds.

Arundathy Nirmalini Pandite: So thank you for the question. With the NLMDS, the monotherapy portion of this is a very short monotherapy. That's our plan to go into the combination very quickly. So we are bringing in an immunologically active dose. We are bridging that dose from the face 1 ovarian study, and our plan is to go quickly into the combinations that I mentioned with ACE-Systitoneone, Benetoclax, and with ASAIDA in Monocera, with exercise again, and to test it in Manito class.

Yes.

Thank you for the question.

Ml Mds monotherapy a portion of this is a very shocked monotherapy.

That's our plan is to go into the combination that quickly.

We are bringing in in an immunologically active dose we're breaching that dose from the phase one ovarian study and our plan is to go quickly into the combinations that I mentioned that <unk> decided that they need to collect and with Azacitidine monotherapy.

And with <unk> and its entertainment Interconnects.

Operator: Okay, sure. So I think that there's no expectation of seeing substantial monotherapy activity there or developing in that direction. Now, if you don't mind, John, I'll just make one quick comment on that point.

Okay.

I take it that there is no expectation of a modest but seeing substantial monotherapy activity there we're developing in that direction.

Yeah.

Yes.

If you don't mind, John I'll, just make one quick comment on that.

Operator: comment on that point. And, you know, our guidance around monotherapy antitumor activity for 172-154 is based on Tuesday is based upon what is known clinically about the expected monotherapy activity of the CD-40 agonist, as well as what is known clinically about the expected activity of an FC silent CD-47 inhibitor. And our interpretation of, you know, the 20 plus years of experience we have had with CD40 agonist antibodies in human clinical studies is that while some agents have shown sporadic monotherapy activity in tumors like melanoma, renal cell carcinoma, and lymphoma, there is no consistent pattern of monotherapy activity, at least with the CD40 agonist antibodies.

<unk>.

And.

Well our guidance around monotherapy antitumor activity for 170.154 is based upon two things.

It's based upon what is known clinically.

About the expected monotherapy activity of the CD 40 agonist as well as what is known clinically about the expected activity of an FC silent CD 47 inhibitor.

And our interpretation of the 20 plus years' experience, we have the CD 40 agonist antibodies in human clinical studies.

While some agents have shown sporadic monotherapy activity in tumors like melanoma renal cell carcinoma in lymphoma.

There is no consistent pattern of monotherapy activity at least with the CD 40 agonist antibodies.

Operator: And because of that, we don't feel that it's appropriate to frame efficacy expectations around any CD40 agonist agent. On the CD47 side, the only agents that have shown monotherapy activity are those that have residual function in the EPSC domain. CD-47 inhibitor agents which lack that function do not have monotherapy activity, and they also don't talk. And so what that tells you about the CD47 inhibitors as a class is that the FC domain and the characteristics of the FC domain are, in and of themselves, sufficient to drive toxicity.

And because of that we don't feel that it's appropriate to frame efficacy expectations around any CD 40 agonists.

Hi.

Jim.

On the <unk> 47 side.

Only agents that have shown monotherapy activity are those that have residual function in the FC domain.

<unk> 47, and inventory agents, which lacked that function.

Do not have monotherapy activity and they also don't have talks.

And so what that tells you with <unk> seven inhibitors as a class is that.

The FC domain and the characteristics of the FC domain are in and of themselves sufficient to drive toxicity.

Operator: However, what you notice about all CD-47 inhibitors, regardless of whether the FCD domain is active or inactive, is that they are all pursuing registrational pathways in combination, either with certain chemotherapies or ADCP competent tumor-targeted antibodies. And so you can then extend the conclusion a bit from there and say that while the FC domain is sufficient for talks and sporadic monotherapy activity, it is insufficient to drive registration. And so with this agent, we are again framing.

However, what you'll notice about all CD 47 inhibitors, regardless of whether the FC domain is active or inactive is that theyre all pursuing registrational pathways in combination either with certain chemotherapies or.

ADP competent tumor targeted antibodies.

And so you can then extend the conclusion a bit from there and say that while the FC domain is sufficient for talks and sporadic monotherapy activity there is insufficient to drive registration.

So with this agent we are again framing expectations based upon 171 five for being a CD 47 inhibitor with an inactive FC domain.

Operator: Great, thank you. I think it's very responsible.

Operator: Maybe turning to 252, can you speak a little bit to the clinical relevance of Ox40 simulation pushing T-cells into the periphery out of the blood? Are there other signs of T-cell activation that go along with that? And granted, it's tough to disambiguate what's going on, given the lack of BL1's activity in many of these patients. But I'm trying to focus specifically on Ox 40-Axus PD and, you know, and what that can tell us.

Great. Thank you.

I think that's very responsive.

Maybe turning to 252.

Can you speak a little bit to the clinical relevance of our ox 40 stimulation pushing two doses into the periphery, rather out of blood or there are other signs of T cell activation that go along with that.

It's tough to figure out what's going on given the lack of deal activity in many of these patients.

I'm trying to focus specifically on almost 40 axis P D and what that can tell us about a successful immuno stimulation.

Operator: access PD and what that can tell us about successful immunos simulations. Yeah, thanks for the question, John.

Yeah. Thanks for the question John.

Operator: So, you know, Ox 40 is an antigen-dependent CD4-specific T-cell co-stimulator, and so you expect the pharmacodynamic, or at least the direct pharmacodynamic effects of box 40 stimulation to be centered on that T-cell population. And more specifically to a subset of CD4 positive box 40 positive T cells that are actively encountering, in this case, tumor antigen. And in that subset of cells, you may expect those cells to rapidly carry 279252 from the peripheral blood into tissue.

So ox 40, as a as an antigen dependent CD four specific T cell co stimulator.

And so you expect the pharmacodynamic at least the direct pharmacodynamic effects of ox 40 stimulation to be centered on that T cell population and more specifically to <unk>.

As subset of CD four positive <unk> positive T cells that are actively encountering in this case tumor antigens.

And.

In that subset of cells you.

I expect those cells to rapidly Kerry.

$2.79 to $5 two from the peripheral blood into tissues.

Operator: And if that includes tumor tissues, then that could provide a means of actively transporting 279252 out of the blood and into interpheral tissues, including tumors. And if those cells are being activated, then you would expect to see some signs of that. That could come in the form of changes to the immunopinotipic profile of those cells, patterns of activation markers, or it could come in other forms. But it's hard to know for sure because the human experience with ox 40 antibodies has shown very, very little in the way of convincing pharmacodynamic activity to date.

And if that includes tumor tissues then.

That could provide a means of actively transporting two 795, two out of the blood and into peripheral tissues, including tumors.

And if those cells are being activated then you would expect to see some signs of that.

That could come in the form of.

Changes to the immuno phenotypic profile of those cells.

Patterns of.

Activation markers.

Or it could come in other forums, but.

It's hard to say for sure because.

The human experience with ox 40 antibodies.

Contains very very little in the way of convincing pharmacodynamic activity to date.

Operator: And so I think we are in somewhat uncharted territory here for Ox 40 Aganus, and therefore we want to be sure that we fully explore the dose levels here and identify a dose level at which Oxford Biology, at least as far as we can measure it, has been maxed out.

And so I think we are.

And in somewhat uncharted territory here for ox 40 agonists.

And therefore.

We want to be sure that we fully explore.

The dose levels here and identify the dose level at which ox 40 biology at least as far as we can measure it.

Operator: Great, it makes sense. Thank you very much.

<unk> has been maximized.

Operator: Our next question is on the Comfort line from Gil Brum from Neatham. You may begin.

Great makes sense. Thank you very much.

Our next question will come from the line.

Operator: And congratulations on all the progress.

Gil Blum from Needham you may begin.

Operator: Congratulations on all the progress. It looks like the vote programs seem to be very safe. But as your dose escalates, do you expect at some point to start seeing some level of immune-mediated talk, you know, the sort of low-grade rash, and low-grade CRS that we sometimes see with the immune oncology agents? Sure, thanks for the question. I'll ask Lenny to take this one.

Oh and congrats on all the progress.

It looks like the.

Both programs seem to be very safe.

But as you dose escalate do you expect at some point to start seeing some.

Level of immune mediated talks job you know the sort of low grade rash low grade Crs are seeing sometimes with immuno oncology agents.

Sure. Thanks for the question I'll ask Lenny to take this one.

Operator: Yes, as we do escalate, given that we do have an agonist in this molecule as well, we would expect to see some degree of top. What we are very encouraged is that we are able to dose escalate through the lower doses, especially in the CD40, targeted with CD40 antibodies, where dose limiting toxicity has precluded dose escalation beyond 0.3 milligrams per kilogram. We've been able to dose escalate, you know; we are currently at 3 milligrams per kilogram, and so it gives us an opportunity to dose escalate to the point where we have receptor occupancy on both CD-40 as well as CD-47 and are able to saturate those receptors.

Yes, as we dose escalate given that we do have an agonist and this molecule as well.

To see some particularly uptalk. What we are very encouraged that we are able to dose escalate to the lower doses, especially in the CD 40.

Tom.

For the antibody dose limiting toxicity has peak load that dose escalation beyond.

10 milligrams per kilogram that we've been able to dose escalate.

We are currently at three milligrams per kilogram and so it gives us an opportunity to dose escalate to the point that we have.

Occupancy unfolds, CD 40, as well as <unk> 47, and being able to saturate those receptors.

Operator: So I think we're encouraged by this dose escalation that we're able to do. But as you said, there are certainly, I mean, we certainly monitor patients with the view to the fact that there could be toxicity at higher doses.

Encouraged by this dose escalation that we're able to do.

Yeah.

Secondly, I mean, we sell.

Suddenly monetize patients.

Due to the fact that that could be toxicity at higher doses.

Operator: Okay, and on 252, just to clarify that I understood this correctly, so we're discussing enrichment for patients who are PD1 positive and PD1 refractory following PD1 based therapy. Is that correct?

Okay.

And on two sides to just to clarify that I understood. This correctly. So we're discussing enrichment for patients who are <unk> positive.

And PD one refractory following PD one base therapy is that correct.

Operator: Yes, that's correct. That's right.

Yes, that's correct.

That is correct. So the reason for that.

Those escalation up to now we did not select for patients.

PDL one positive.

We started at the very low dose and we wanted to get through the dose escalation.

As efficiently as possible to a point that we can't had an immunologically active dose range and currently we are at that dose range.

But our plan is to select patients with PDL, one positivity and the reason for that is that one and upon molecule.

<unk> PDL, one and so it would make sense to actually select but that's now we certainly acknowledge that these are patients who have failed PD one PD, one therapies and have either.

Any sense of resistance that may preclude them from responding to agents such as that.

Operator: That makes a lot of sense. And maybe our last one on the Pitchiege program, which we haven't discussed.

Okay that makes that makes a lot of sense.

And maybe a last one on the chip program, which we haven't discussed too much today.

Operator: Which we haven't discussed too much today. Following kind of the results in the space, you know, Arcus and others, has there been any, you know, additional disclosures regarding whether, uh, we're going with an SC active or an SC inactive here? There has not been any additional disclosure yet, but we will be providing additional guidance around the next ARC program to enter the clinic later this year.

Following kind of the results in the space ARCUS and others has there been any you know additional disclosures regarding whether we're going with it and that's the active or inactive here.

Okay.

There has not been any additional disclosure, yet, but we will be providing additional guidance.

Around the next our program to enter the clinic.

Operator: Okay, excellent. And we all definitely look forward to your results at SETC. Thank you for taking our questions.

Later this year.

Okay excellent.

I'll definitely look forward for your results. Thank you for taking our questions.

Operator: And the last question will come from Kwan Shui from Bamberg. You may begin.

Thanks for the questions.

And our last question will come from the line of the corn shrink from Banbury you may begin.

Operator: Hi, good afternoon. Thanks for taking my question.

Hi, good afternoon, Thanks for taking my question.

Operator: So on your first 154 program, your current dose is 3, 3 milligrams.

So on your first one 504 program.

The the kind of dosing is three 3 million.

Operator: 3 milligrams, the kilogram, the next one is 10. It seems to be a big jump. I guess what gives you that level of comfort, you can, those escalate to more than two, three times the amount that you currently are.

Graham can there Brian because you the next one.

They seem to be a big jump I guess, what what gives you the.

That level of comfort you can dose escalate to one.

Operator: Sure, IZ, thanks for the question. I'll ask her later.

Two three times of that that gives you kind of dose.

Operator: me to take that one as well.

Okay.

Sure. Thanks for the question I'll ask Tony to take that one as well.

Operator: Zee, we often dose escalate in these oncology studies by half-long increments. So that three to ten is a reasonable increase; that's a half-lock increase. And depending on what we see at 10, then we'll determine whether we need to go higher or not. But right now, that's actually a very reasonable increase.

Boston dose escalate in these oncology studies and have locked in claims.

So that <unk> 10 is a reasonable increase.

Increased that to half load increase.

And so depending on what we see.

10, and we'll determine whether we need to go higher or not.

Now thats actually a very reasonable increase.

Operator: Got it. And then, in terms of the next step, we select a recommended phase two dose and move into the combination study, a combination phase of the study. I guess what a gating factor you will be looking for when you select the dose and when you want to combine it with retoxymite.

Got it and then in terms of next step we select a recommended phase two dose and move into the combination.

Ah study.

That's a combination of phase of the study I guess, what I wanted.

<unk> factors in Europe, we're looking for ways, where you where you select the.

And it goes and where you want to comply with the SEC.

Operator: Takamab, you are a rich man... I mean,

Rituxan.

Can you talk to my view our yard.

Operator: Sure. So, in general, what we're looking for in identifying a recommended phase two dose is to find a dose that is well-colerated where we see saturation of both targets of the arc compounds. So in the case of 17215, 4, that will mean saturation of both CD-47 and CD-40, and where we see that there has been a continued escalation in the on-target pharmacodynamic effects that we expect to see downstream of that engagement, and wherein those pharmacodynamic effects have escalated up to a point and then reached a plateau.

Okay.

In the trial.

Sure So in general.

What we're looking for in identifying a recommended phase II dose.

As defined.

A dose which is well tolerated.

Where we see saturation of both targets.

Of the arc compounds. So in the case of 171% floor that will mean saturation, both SEC 47, and <unk> 40.

And where we see that.

There has been a continued escalation in the on target Pharmacodynamic effects that we expect to see downstream of that engagement and we're in those pharmacodynamic effects of escalated up to a point and then reached a plateau.

Operator: Presumably, after, you know, not every patient will reach maximum pharmacodynamic activation of CD40 or Ox 40 at the exact same dose. And so identification of a maximum plateau may improve the probability that we select a dose which maximizes the biology for all patients we might treat. Of course, then observation of antitumor activity is important. And we should have mentioned this earlier, but also in narrowing the dose and schedule, we'll be looking as well at the PK profile and ensuring that not only do we achieve full occupancy of the targets but that there is sufficient free drug in the system to maintain full occupancy through the dosing interval. So collectively, those are the vectors that we're triangulating to pick a dose going into subsequent studies.

Presumably after you know not every patient will reach maximum pharmacodynamic.

Activation of CD 40, or ox 40.

At the exact same dose and so identification of a maximum plateau may improve the probability there'll be selected dose, which maximizes the biology, where all patients we might treat.

Of course, then observation of antitumor activity.

As important.

And then we should've mentioned this earlier, but also.

And narrowing the dose and schedule.

We will be looking as well as the PK profile and ensuring that not only do we.

Achieve full occupancy of the targets, but that there is sufficient free drug in the system to maintain full occupancy through the dosing interval.

So collectively those are.

The vectors that we're triangulating to pick a dose going into subsequent studies.

Great. Thanks Tyler.

Sure. Thanks for the question.

Thank you.

So all the time, we have for today's Q&A session of the call.

At this time I would like to turn the call back over to Taylor Shredder.

Taylor H. Schreiber: Thank you, operator, and thank you all for joining the Shattuck Lab's second quarter financial results and business updates conference call. We appreciate your continued interest in Shattuck, and we look forward to updating you on our milestones throughout the remainder of this year. Thanks very much.

I'm sorry.

Closing remarks.

Thank you operator, and thank you all for joining the <unk> second quarter financial results and business update conference call.

We appreciate your continued interest in <unk> and we look forward to updating you on our milestones throughout the remainder of this year. Thanks very much.

Operator: This includes today's conference call. Thank you for participating. You may now disconnect. Have a wonderful day.

This concludes today's conference call. Thank you for participating you may now disconnect have a wonderful day.

Q2 2021 Shattuck Labs Inc Earnings Call

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