Q2 2024 Crinetics Pharmaceuticals Inc Earnings Call

Speaker Change: Robert Newcomen Jones zijn Bruno van de Brin, Carlos Capurini, The Lodge police, Brian Six, It's just a small community, and it's about double either good or good. The only good one is certainly the one I like. The only reason I like it is because at every once in a couple of years the three-year-old, that's what they call her, is haven't easily gotten by the police. It's just a community of everyoneulse and we kind of live by it, but the rest is brewing, because everybody's kids or family, they've got to pick something out for themselves on a regular basis. Every time they're moving they're picking something for themselves and really picking others up.

Operator: Please stand by; your program is about to begin. If you need assistance with today's program, please press star zero.

Please stand by. Your program is about to begin. If you need assistance on today's program, please press star zero.

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unknown: The Bulletproof Executive, 2013

Speaker Change: music

Unknown Executive: Good day, everyone, and welcome to the Crinetics Pharmaceuticals second quarter 2024 earnings conference call. At this time, all participants are any listed in only mode. Later, you will have the opportunity to ask questions during the question-and-answer session. You may register to ask a question at any time by pressing the star in one on your telephone keypad. You may withdraw yourself from the queue by pressing star two.

Operator: Good day, everyone, and welcome to the Crinetics Pharmaceuticals second quarter 2024 earnings conference call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question and answer session. You may register to ask a question at any time by pressing the star and one on your telephone keypad. You may withdraw yourself from the queue by pressing star two. Please note, this call may be recorded. I'll be standing by should you need any assistance. It is now my pleasure to turn the program over to Gaia Three DeWalker.

Speaker Change: Good day, everyone, and welcome to the Crinetics Pharmaceuticals second quarter 2024 earnings conference call.

Speaker Change: At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question and answer session.

Speaker Change: You may register to ask a question at any time by pressing the star and 1 on your telephone keypad. You may withdraw yourself from the queue by pressing star 2. Please note this call may be recorded. I'll be standing by should you need any assistance. It is now my pleasure to turn the program over to Gaia 3 DeWalker.

Unknown Executive: Please note this call may be recorded. I'll be standing by. Should you need any assistance?

Gaia III DeWalker: It is not my pleasure to turn the program over to Gaia III DeWalker.

Scott Strothers: Thank you, operator.

Gaia Three DeWalker: Thank you, operator. Hello, everyone, and welcome to Crinetics' Earning Call. Joining me today are Dr. Scott Struthers, Founder and Chief Executive Officer, Dr. Dana Pizzuti, Chief Medical and Development Officer, Jim Hassard, Chief Commercial Officer, and Marc Wilson, Chief Financial Officer. Also joining us for the Q&A portion of the call is Dr. Alan Krasner, Chief Endocrinologist.

Scott Strothers: Hello everyone and welcome to Crinetics' earning call. Joining me today are Dr. Scott Strothers, founder and Chief Executive Officer. Dr. Dana Pizzuti, Chief Medical and Development Officer, Jim Hazard, Chief Commercial Officer, and Marc Wilson, Chief Financial Officer. Also joining us for the Q&A portion of the call is Dr. Alan Krasner, Chief Under Chronologist.

Speaker Change: Thank you, Operator. Hello, everyone, and welcome to Crinetics' Earning Call.

Speaker Change: Joining me today are Dr. Scott Struthers, Founder and Chief Executive Officer, Dr. Dana Pizzuti, Chief Medical and Development Officer, Jim Hassard, Chief Commercial Officer, and Marc Wilson, Chief Financial Officer.

Speaker Change: Also joining us for the Q&A portion of the call is Dr. Alan Krasner, Chief Endocrinologist.

Scott Strothers: Approximately announcing the second quarter, 2024 financial results was issued today and is also available on our corporate website. We will be using slides for today's presentation, which can be viewed on the Investor Relations section of the Crinetics website. As a reminder, we'll be making forward-looking statements and invite you to learn more about the risks and uncertainties associated with these statements as disclosed in our SEC filing. Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those stated or implied in substatements due to risks and uncertainties associated with the company's business.

Gaia Three DeWalker: A press release announcing the second quarter 2024 financial results was issued today and is also available on our corporate website. We will be using slides for today's presentation, which can be viewed in the Investor Relations section of the Crinetics website. As a reminder, we'll be making forward-looking statements, and I invite you to learn more about the risks and uncertainties associated with these statements as disclosed in your SEC filing. Such forward-looking statements are not guarantees of performance, and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business.

Speaker Change: A press release announcing the second quarter 2024 financial results was issued today and is also available on our corporate website. We will be using slides for today's presentation, which can be viewed on the Investor Relations section of the Crinetics website.

Speaker Change: As a reminder, we'll be making forward-looking statements, and I invite you to learn more about the risks and uncertainties associated with these statements as disclosed in your SEC filing.

Speaker Change: Such forward-looking statements are not a guaranteed performance, and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business.

Scott Strothers: These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release, the company's other news releases, and the Crinetics SEC filing, including its annual report on Form 10-K.

Gaia Three DeWalker: These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release, the company's other news releases, and the Crinetics SEC filings, including its annual report on Form 10-K. I would also like to specify that the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, August 8, 2024. Crinetics undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call.

Speaker Change: These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release, the company's other news releases, and the Crinetics SEC filings, including its annual report on Form 10-K .

Scott Strothers: I would also like to specify that the content of this conference call contains time-sensitive information that's accurate only as the date of this live broadcast, August 8, 2024. Crinetics takes your obligation to revise or update any forward-looking statements to flip events or circumstances after the date of this conference call.

Speaker Change: I would also like to specify that the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, August 8, 2024.

Speaker Change: Crinetics takes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. With that, I'll hand the call over to Scott.

Scott Strothers: Without, I'll hand the call over to Scott.

Scott Struthers: Thank you, Gaffrey. Good afternoon, everyone, and thank you for joining us on our second quarter 2024 results call. I'll begin by spending a few moments summarizing our recent accomplishments, then I will hand the call over to Dr. Dana Pizzuti, our Chief Medical and Development Officer, who will provide a regulatory update. Jim Hazzard, our Chief Commercial Officer, will share our plans to bring our lead candidate paltustine to patients, and Marc Wilson, our Chief Financial Officer, will wrap up with a thrilling financial update. The second quarter of 2024 was extremely productive for Crinetics.

Scott Strothers: Thank you, Guy Astrid. Good afternoon, everyone, and thank you for joining us on our second quarter 2024 results call. I'll begin by spending a few moments summarizing our recent accomplishments.

Scott Struthers: With that, I'll hand the call over to Scott. Thank you, Gayathri. Good afternoon, everyone.

Scott: Thank you, Gayathri. Good afternoon, everyone, and thank you for joining us on our second quarter 2024 results call.

Scott Strothers: Then, I will hand the call over to Dr. Dana Pizuti, our Chief Medical and Development Officer, who will provide a regulatory update. Jim Hazard, our Chief Commercial Officer, will share our plans to bring our lead candidate, Peltus, team to patients.

Scott: I'll begin by spending a few moments summarizing our recent accomplishments. Then I will hand the call over to Dr. Dana Pizzuti, our Chief Medical and Development Officer, who will provide a regulatory update.

Scott: Jim Hazzard, our Chief Commercial Officer, will share our plans to bring our lead candidate paltustine to patients, and Marc Wilson, our Chief Financial Officer, will wrap up with a thrilling financial update.

Scott Strothers: Mark Wilson, our Chief Financial Officer, will wrap up with a thrilling financial update. The second quarter of 2024 was extremely productive for Crinetics. The Endocrine Society Annual Meeting in June proved to be an impactful meeting for us. We were thrilled to share highly encouraging initial results from the ongoing phase two studies of our second development candidate, Atumelna, in both congenital adrenal hyperplasia and Cushing's. Disease. These unprecedented data were very well received by the under-conology community. This reinforced our already strong confidence in the potential of ATEML-NAT to be a best in class and first in class agent in both indications.

Scott: The second quarter of 2024 was extremely productive for Crinetics.

Scott Struthers: The Endocrine Society Annual Meeting in June proved to be an impactful meeting. We were thrilled to share highly encouraging initial results from the ongoing Phase 2 studies of our second development candidate, Atum Elnam, in both congenital adrenal hyperplasia and Cushing's disease. These unprecedented data were very well received by the endocrinology community.

Scott: The Endocrine Society annual meeting in June proved to be an impactful meeting for us.

Scott: We were thrilled to share highly encouraging initial results from the ongoing Phase 2 studies of our second development candidate, Atomelna, in both congenital adrenal hyperplasia and Cushing's disease.

Scott: These unprecedented data were very well received by the endocrinology community.

Scott Struthers: This reinforced our already strong confidence in the potential of Actimelnet to be a best-in-class and first-in-class agent in both indications. Patients need better therapeutic options, and we are committed to realizing atumelan's full potential as a revolutionary new treatment paradigm for people suffering from CAH and Cushing's disease. The Crinetics team is working hard to move the development of adenine forward in both indications and bring this potential therapy to people around the world. We also presented data from Paltucetine's Pathfinder Phase 3 acromegaly program at ENDO.

Scott: This reinforced our already strong confidence in the potential of FMLNet to be a best-in-class and first-in-class agent in both indications.

Scott Strothers: Cations need better therapeutic options, and we are committed to realizing ATEML-NAT's full potential as a revolutionary new treatment paradigm for people suffering from CH and Cushing's disease. Crinetics team is working hard to move development of ATEML-NAT for it in both indications and bring this potential therapy to people around the world. We also presented data from Paltusa Team's Pathfinder Phase 3 Acromegaly Program at Endo. A new analysis from Pathfinder 1 highlights results, highlighted results from an exploratory analysis using patient-reported outcomes captured in the Acromegaly Symptom Diary or ASD. These data showed that patients on monthly standard of care injections were defined as biochemically controlled, actually experienced variable variability in symptom control.

Scott: Patients need better therapeutic options and we are committed to realizing Atomelanth's full potential as a revolutionary new treatment paradigm for people suffering from CAH and Cushing's disease.

Speaker Change: Chronetic's team is working hard to move development of atinine forward in both indications and bring this potential therapy to people around the world.

Scott: Thank you very much for watching this video.

Speaker Change: We also presented data from Paltucetine's Pathfinder Phase III acromegaly program at Endo.

Scott Struthers: A new analysis from Pathfinder 1 highlights results from an exploratory analysis using patient-reported outcomes captured in the Acromegaly Symptom Diary, or ASD. These data show that patients on monthly standard-of-care injections, who are defined as biochemically controlled, actually experience variable variability in symptom control.

Speaker Change: A new analysis from Pathfinder 1 highlights results, highlighted results from an exploratory analysis using patient-reported outcomes captured in the Acromegaly Symptom Diary, or ASD.

Speaker Change: These data show that patients on monthly standard of care injections, who are defined as biochemically controlled, actually experience variable variability in symptom control.

Scott Strothers: In contrast, once daily Paltusa Team was associated with stable biochemical control and low rates of breakthrough symptoms. Dana and Jim will speak a more on our progress of bringing Paltusa Team patients, but I'm incredibly excited about its potential to transform the future of Acromegaly treatment and to find a new standard of care.

Scott Struthers: In contrast, once-daily paltucinine treatment was associated with stable biochemical control and low rates of breakthrough symptoms. Jim, Dana, and Jim will speak more about our progress of bringing Pelticine to patients, but I'm incredibly excited about its potential to transform the future of acromegaly treatment and define a new standard of care. Overall, our 2024 plans remain on track.

Speaker Change: In contrast, once-daily paltucetine treatment was associated with stable biochemical control and low rates of breakthrough symptoms.

Speaker Change: Jim and Dana and Jim will speak more on our progress of bringing Pelticine to patients, but I'm incredibly excited about its potential to transform the future of acromegaly treatment and define a new standard of care.

Scott Strothers: Overall, our 2024 plans remain on track. Our next steps this year include filing the Paltusa Team NDA for Acromegaly, engaging with regulators to align on the initiation of a Phase 3 program in carcinoid syndrome, completing the Phase 2 studies of FMLNF and CAH and Cushing's, and transitioning multiple new drug candidates from our discovery efforts into pre-clinical and IND-enabling development. Along these lines, we've continued to make meaningful progress on our early stage pipeline. First, we've identified a parathyroid hormone or PTH receptor antagonist development candidate for our hyperparathyroidism program. Pre-clinical data demonstrate that this candidate reduces both PTH and PTH-related protein-induced hypercalcemia in rodent models, and it possesses a favorable drug-like profile.

Speaker Change: www.thevenusproject.com

Scott Struthers: Our next steps this year include filing the Peltucetine NDA for acromegaly, engaging with regulators to align on the initiation of a phase three program in carcinoid syndrome, completing the Phase II studies of FMLNAT and CAH in Cushing's, and transitioning multiple new drug candidates from our discovery efforts into preclinical and IND-enabling development. Along these lines, we've continued to make meaningful progress in our early stage pipeline. First, we identified a parathyroid hormone or PTH receptor antagonist.

Speaker Change: Overall, our 2024 plans remain on track.

Speaker Change: Our next steps this year include filing the Peltucetine NDA for Acromegaly, engaging with regulators to align on the initiation of a Phase III program in carcinoid syndrome,

Speaker Change: completing the phase 2 studies of etimelinat and CAH in Cushing's, and transitioning multiple new drug candidates from our discovery efforts into preclinical and IMD-enabling development.

Speaker Change: Along these lines, we continue to make meaningful progress on our early stage pipeline.

Speaker Change: First, we've identified a parathyroid hormone, or PTH, receptor antagonist development candidate for our hyperparathyroidism program.

Scott Struthers: Development Candidate for our Hyperparathyroidism Program. Preclinical data demonstrate that this candidate reduces both PTH and PTH-related protein-induced hypercalcemia in rodent models, and it possesses a favorable drug-like profile that is likely consistent with once-per-day dosing in humans.

Speaker Change: Preclinical data demonstrates that this candidate reduces both PTH and PTH-related protein-induced hypercalcemia in rodent models, and it possesses a favorable drug-like profile.

Scott Strothers: This profile is likely consistent with once-per-day dosing in humans. We've begun IND-enabling studies in anticipation of filing an IND in 2025.

Speaker Change: This profile is likely consistent with once-per-day dosing in humans.

Scott Struthers: We've begun IND-enabling studies and anticipate filing an IND in 2025. We've also selected an SST3 agonist development candidate to explore a completely new mechanism for the treatment of autosomal dominant polycystic kidney disease, or ADPKD. Sorry, I lost my place.

Speaker Change: We've begun IND-enabling studies and anticipate filing an IND in 2025.

Scott Strothers: We've also selected an SST-3 agonist development candidate to explore a completely new mechanism for the treatment of autosomal dominant polycystic kidney disease or ADPKD. ADPKD, excuse me, lost my place. ADPKD is one of the most common genetic diseases and affects over 140,000 people in the U.S. Pre-clinical data for this candidate are very promising, and we are pursuing options to advance this program to clinical studies either with a partner or independently.

Speaker Change: We've also selected an SST3 agonist development candidate to explore a completely new mechanism for the treatment of autosomal dominant polycystic kidney disease, or ADPKD.

Speaker Change: ADPKD

Speaker Change: Excuse me.

Scott Struthers: ADPKD is one of the most common genetic diseases and affects over 140,000 people in the U.S. Preclinical data for this candidate are very promising, and we are pursuing options to advance this program to clinical studies, either with a partner or independently. Our discovery programs for Graves' disease, Discovery Program for Graves' Disease, including thyroid eye disease, and obesity, continue to make great progress, and we look forward to announcing Optimized candidates for these programs in the near future.

Speaker Change: Last night, please.

Speaker Change: ADPKD is one of the most common genetic diseases and affects over 140,000 people in the U.S.

Speaker Change: Preclinical data for this candidate are very promising and we are pursuing options to advance this program to clinical studies either with a partner or independently.

Scott Strothers: Our discovery programs for graze disease Discovery Program for Grace Disease including thyroid eye disease and obesity continue to make great progress, and we look forward to announcing optimized candidates for these programs in the near future. As a reminder, our pipeline also includes novel molecules and technologies that are being developed by our partners. For example, several years ago, we developed a novel non-peptide radiotherapy agnostic program that could be used in multiple oncology indications. With this, we created a company around the technology called Radionetics Oncology and entered into a collaboration and license agreement with the company. Radionetics announced on July 1st that it entered into a strategic relationship with Eli Lilly and Company.

Speaker Change: Our Discovery Program for Graves' Disease, including thyroid eye disease and obesity, continue to make great progress, and we look forward to announcing optimized candidates for these programs in the near future.

Scott Struthers: As a reminder, our pipeline also includes novel molecules and technologies that are being developed by our partners. For example, several years ago, we developed a novel non-peptide radiothera-agnostic program that could be used in multiple oncology indications.

Speaker Change: As a reminder, our pipeline also includes novel molecules and technologies that are being developed by our partners.

Speaker Change: For example, several years ago we developed a novel non-peptide radiothera-agnostic program that could be used in multiple oncology indications.

Scott Struthers: With this, we created a company around the technology called Radionetics Oncology and entered into a collaboration and license agreement with the company. Radionetics announced on July 1st that it entered into a strategic relationship with Eli Lilly & Co. Under the terms of the agreement, Radionetix received $140 million up front, and Lilly obtained a warrant for the exclusive right to purchase Radionetix for $1 billion. Crinetics currently owns approximately 25% of Radio Netta.

Speaker Change: With this, we created a company around the technology called Radionetics Oncology and entered into a collaboration and license agreement with the company.

Speaker Change: RadioNetflix announced on July 1 that it entered into a strategic relationship with Eli Lillian Company.

Scott Strothers: Under the terms of the agreement, Radionetics received $140 million upfront, and Lily obtained a warrant for the exclusive right to purchase Radionetics for one billion. Chronetics currently owns approximately 25% of Radionetics. If Lily were to exercise its right to purchase Radionetics, Chronetics would receive its pro-rata share of the $1 billion purchase price. Chronetics is also entitled to single digital royalties and commercialization milestones for the three programs currently in development of Radionetics.

Speaker Change: Under the terms of the agreement, radionetics receives $140 million up front and lily obtained a warrant for the exclusive right to purchase radionetics for one billion.

Speaker Change: Kronetics currently owns approximately 25% of radio networks.

Scott Struthers: If Lilly were to exercise its right to purchase Radionetics, Crinetics would receive its pro-rata share of the $1 billion purchase price. Crinetics is also entitled to single-digit royalties and commercialization milestones for the three programs currently in development at Radionetics. We believe this transaction is a great validation of the strength of our discovery platform and has the potential to generate non-dilutive funding for Crinetics in the future. We also have a partnership with Lowe's, in which we license another one of our targeted somatostatin molecules to extend the lifespan and healthspan of dogs.

Speaker Change: If Lily worked to exercise its right to purchase radionetics, Krenetics would receive its pro-rata share of a $1 billion purchase price.

Speaker Change: Crinetics is also entitled to single-digit royalties and commercialization milestones for the three programs currently in development at Radionetics.

Scott Strothers: We believe this transaction is a great validation of the strength of our discovery platform and has the potential to generate non-divisive funding for kinetics in the future.

Speaker Change: We believe this transaction is a great validation of the strength of our discovery platform and has its potential to generate non-dividive funding from networks in the future.

Scott Strothers: We also have a partnership with Wood, in which we license another one of our targeted Somatos Fountain molecules to extend the lifespan and health span of dogs. The company, the entire company, is hard at work executing our strategy to help more patients with endocrine-related diseases and to build long-term value for Kinetics shareholders.

Speaker Change: We also have a partnership with LODD, in which we license another one of our targeted somatostatin molecules to extend the lifespan and healthspan of dogs.

Scott Struthers: The company, the entire company, is hard at work executing our strategy to help more patients with endocrine-related diseases and to build long-term value for chronetic shareholders. Lastly, as you may have seen in our press release, Marc, our Chief Financial Officer, will be leaving the company for personal reasons. The Crinetics executive team and board are grateful for Marc's contributions to the company as he has been an invaluable member of the Crinetics team since before the IPO.

Speaker Change: The company, the entire company is hard at work executing our strategy to help more patients with endocrine related diseases and to build long-term value for chronetic shareholders.

Scott Strothers: Lastly, as you may have seen in our press release, Mark, our Chief Financial Officer, will be leaving the company for personal reasons. The Chronetics executive team in board are grateful for Mark's contributions to the company, as he has been an invaluable member of the Chronetics team since before the IPO. His leadership was instrumental in the success of all our public market activities, which have put Chronetics on a strong financial footing. We've initiated a search for a successor, and Mark will remain in his current position until a successor is onboarded to ensure a seamless transition.

Speaker Change: Lastly, as you may have seen in our press release,

Speaker Change: Mark, our Chief Financial Officer.

Mark: We'll be leaving the company for personal reasons.

Speaker Change: The Kronetics executive team and board are grateful for Marc's contributions to the company, as he has been an invaluable member of the Kronetics team since before the IPO.

Scott Struthers: His leadership was instrumental in the success of all our public market activities, which have put Crinetics on a strong financial footing. We've initiated a search for a successor, and Marc will remain in his current position until a successor is onboarded to ensure a seamless transition. With that, I'll hand it over to Dr. Dana Pizzuti to discuss our clinical and regulatory progress in more detail.

Speaker Change: His leadership was instrumental in the success of all our public market activities, which have put Crinetics on a strong financial footing.

Speaker Change: We've initiated the search for successors and Michael remaining his current position until a successor is onboarded to ensure a seamless transition.

Dana Pizzuti: With that, I'll hand it over to Dr. Dana Favuti to discuss our clinical and regulatory progress in more detail.

Dana Pizzutti: With that, I'll hand it over to Dr. Dana Pizzuti to discuss our clinical and regulatory progress in more detail. Thank you, Scott.

Dana Pizzuti: Dana. Thank you, Scott. I'll start with our lead candidate, Paltuzatin. As Scott just mentioned, we remain on track to submit our NTA for Paltuza for treatment in its first indication, acromegaly, this year. As we have discussed, the Phase III Pathfinder Program was designed to evaluate the safety and efficacy of paltuzatine for the treatment of a broad spectrum of patients with acromegaly. Based on the success of both Phase III Pathfinder studies, we intend to seek approval for all patients, including those switching from the standard of care injected SRLs to paltuzatine as studied in Pathfinder I and those who are not currently treated as studied in Pathfinder In parallel with our Phase III program, we have laid the foundation to streamline and accelerate the NDA filing process.

Dana Pizzuti: Thank you. Thank you, Scott.

Dana Pizzuti: I'll start with our lead candidate, Paltuza team. As Scott just mentioned, we remain on track to submit our NTA for Paltuza team in its first indication, acromegaly, this year. As we have discussed, the phase three Pathfinder program was designed to evaluate the safety and efficacy of Paltuza team for the treatment of a broad spectrum of patients with acromegaly. Based on the success of both phase three pathfinder studies, we intend to seek approval for all patients, including those switching from the standard of care injected SRLs to Paltuza team, as studied in Pathfinder one, and those who are not currently treated as studied in Pathfinder two.

Dana Pizzutti: I'll start with our lead candidate, Paltuzatine. As Scott just mentioned, we remain on track to submit our NTA for Paltuzatine in its first indication, acromegaly, this year.

Speaker Change: As we have discussed, the Phase III Pathfinder Program was designed to evaluate the safety and efficacy of paltuzatine for the treatment of a broad spectrum of patients with acromegaly.

Speaker Change: Based on a success of both Phase 3 and Pathfinder studies, we intend to seek approval for all patients, including those switching from the standard of care injected SRLs to Balthusity.

Speaker Change: as studied in Pathfinder I and those who are not currently treated as studied in Pathfinder II.

Dana Pizzuti: In parallel with our phase 3 program, we have laid the foundations to streamline and accelerate the NDA filing. We have held two productive pre-NDA interactions with the FDA to align on clinical, non-clinical, CMC, and quality topics. The FDA confirmed that our proposed package supports admission for both the maintenance of aqua-megely. This robust package includes data from our two Pathfinder Phase 3 studies, as well as dose response analyses, data from our long-term safety studies, and patient outcomes from the aqua-megely symptom diary, which showed significant improvements in patient-reported symptoms in both of our studies.

Speaker Change: In parallel with our Phase III program, we have laid the foundation to streamline and accelerate the NDA filing.

Dana Pizzuti: We have held two productive pre-NDA interactions with the FDA to align on clinical, non-clinical, CMC, and quality topics. The FDA confirmed that our proposed package supports admission for both the treatment and maintenance of acromegaly. This robust package includes data from our two Pathfinder Phase III studies, as well as dose-response analyses, data from our long-term safety studies, and patient outcomes from the Acromegaly Symptom Diary, which showed significant improvements in patient-reported symptoms in both of our studies. We look forward to updating you as we continue toward the NDA final.

Speaker Change: We have held two productive pre-NDA interactions with the FDA to align on clinical, non-clinical, CMC, and quality topics.

Speaker Change: The FDA confirmed that our proposed package supports admission for both the treatment and maintenance of acromegaly.

Speaker Change: This robust package includes data from our two Pathfinder Phase III studies, as well as dose response analyses, data from our long-term safety studies, and patient outcomes from the Acromegaly Symptom Diary, which showed significant improvements in patient-reported symptoms in both of our studies.

Dana Pizzuti: We look forward to updating you as we continue towards the NDA file. In addition, we are diligently conducting healthy genomics and outcome studies to further demonstrate the value proposition of Paltuza team in aqua-megely. This work supports the commercial team's efforts as they engage with payers, physicians, and patients.

Speaker Change: We look forward to updating you as we continue towards the NDA final.

Dana Pizzuti: In addition, we are diligently conducting health economics and outcome studies to further demonstrate the value proposition of paltuzatine and acromegaly. This work supports the commercial team's efforts as they engage with payers, physicians, and patients. We are also making progress in paltuzatine's second indication, carcinoid syndrome. As previously reported, our Phase 2 study showed highly statistically significant results demonstrating the potential of paltucetine to treat people living with carcinoid syndrome.

Speaker Change: In addition, we are diligently conducting health economics and outcome studies to further demonstrate the value proposition of paltuzatine and acromegaly. This work supports the commercial team's efforts as they engage with payers, physicians, and patients.

Dana Pizzuti: We are also making progress in Paltuza team's second indication, carcinoid syndrome. As previously reported, our Phase 2 study showed highly statistically significant results demonstrating the potential of Paltuza team to treat people living with carcinoid syndrome. Importantly, the patients who elected to participate in the ongoing open-label extension continue to benefit from Paltuza Team. Building on this success, we are preparing to discuss the Phase 2 results with the FDA and align on the design of a Phase 3 protocol.

Speaker Change: We are also making progress in paltuzatine's second indication, carcinoid syndrome.

Speaker Change: As previously reported, our Phase II study showed highly statistically significant results demonstrating the potential of paltustine to treat people living with carcinoid syndrome.

Dana Pizzuti: Importantly, the patients who elected to participate in the ongoing Open Label Extension continue to benefit from paltucetine. Building on this success, we are preparing to discuss the Phase 2 results with the FDA and align on the design of a Phase 3 protocol. We expect to initiate the Phase 3 trial by the end of 2024. Turning now to Adam Mellman, we are excited about the progress and potential of Adam Mellman in both CAH and Cushing's disease.

Speaker Change: Importantly, the patients who elected to participate in the ongoing Open Label Extension continue to benefit from Paltucetine.

Speaker Change: Building on this success, we are preparing to discuss the Phase II results with the FDA and align on the design of a Phase III protocol. We expect to initiate the Phase III trial by the end of 2024.

Dana Pizzuti: We expect to initiate the Phase 3 trial by the end of 2024.

Dana Pizzuti: Turning now to Adam Melment, we are excited about the progress and potential of Adam Melment in both CAH and Cushing's disease. As Scott mentioned, the initial results from the open-label Phase 2 studies, which were featured at Endo, have exceeded our expectations. The three cohorts evaluating different doses of Adam Melment in the CAH Phase 2 study are now fully enrolled. We anticipate additional data will be available this year, and we are excited to advance this program.

Adam Mellman: Turning now to Adam Mellman, we are excited about the progress and potential of Adam Mellman in both CAH and Cushing's disease.

Dana Pizzuti: As Scott mentioned, the initial results from the Open Label Phase 2 studies, which were featured at Endo, have exceeded our expectations. The three cohorts evaluating different doses of adamelnut in the CAH Phase 2 study are now fully enrolled.

Adam Mellman: As Scott mentioned, the initial results from the open-label Phase 2 studies, which were featured at ENDO, have exceeded our expectations.

Speaker Change: The three cohorts evaluating different doses of adimelments in the CAH Phase 2 study are now fully enrolled.

Dana Pizzuti: We anticipate additional data will be available this year, and we are excited to advance this program. We also expect to share additional data from the ongoing study in ACTH dependent Cushing Central later this year. Crinetics is fundamentally committed to placing patients at the forefront of everything we do. This patient-centric approach is deeply ingrained in the development activities for each of the programs in our pipeline. We actively seek patient input throughout the drug development process.

Adam Mellman: We anticipate additional data will be available this year, and we are excited to advance this program.

Dana Pizzuti: We also expect to share additional data from the ongoing study in ACTH-dependent Cushing's Central later this year.

Adam Mellman: We also expect to share additional data from the ongoing study in ACTH-dependent Cushing's syndrome later this year.

Dana Pizzuti: Prinetics is fundamentally committed to placing patients at the forefront of everything we do. This patient-centric approach is deeply ingrained in the development activities for each of the programs in our pipeline. We actively seek patient input throughout the drug development process. We've gained valuable insights by sharing data with patients, particularly from our ACRMEGALY program. These insights validate our commitment to developing treatments that improve patients' quality of life, such as offering convenient dosing regimens. We have also routinely partnered with patient advocacy groups to obtain patient input on clinical trial design. Patients are enthusiastic about the potential of Paltusateen, recognizing that it not only delivers the desired biochemical control, but can also improve the symptom of the burden associated with their conditions.

Adam Mellman: Crinetics is fundamentally committed to placing patients at the forefront of everything we do. This patient-centric approach is deeply ingrained in the development activities for each of the programs in our pipeline.

Adam Mellman: We actively seek patient input throughout the drug development process.

Dana Pizzuti: We've gained valuable insights by sharing data with patients, particularly from our acromegaly program. These insights validate our commitment to developing treatments that improve patients' quality of life, such as offering convenient dosing regimens. We have also routinely partnered with patient advocacy groups to obtain patient input on clinical trial design. Patients are enthusiastic about the potential of paltusatine, recognizing that it not only delivers the desired biochemical control but can also improve the symptoms of the burden associated with their condition.

Adam Mellman: We've gained valuable insights by sharing data with patients, particularly from our Aquamitaly program.

Adam Mellman: These insights validate our commitment to developing treatments that improve patients' quality of life, such as offering convenient dosing regimens.

Adam Mellman: We have also routinely partnered with patient advocacy groups to obtain patient input on clinical trial design.

Paltu: Patients are enthusiastic about the potential of Paltu's team, recognizing that it not only delivers the desired biochemical control, but can also improve the symptom of the burden associated with their condition.

Dana Pizzuti: We invested considerable effort to develop the acromegaly symptom diary and are supporting that with psychometric analyses to help document the impact of Paltusatine on patients' quality of life.

Dana Pizzuti: We invested considerable effort in developing the acromegaly symptom diary and are supporting that with psychometric analyses to help document the impact of paltuzatine on patients' quality of life. The positive feedback we have received so far indicates that our patient-focused approach can help us develop better therapies that make a meaningful difference to patients. I'll now hand the call over to Jim to review the commercial readiness strategy and current progress. Thank you, Dana.

Adam Mellman: We invested considerable effort to develop the acrolegly symptom diary, and are supporting that with psychometric analyses to help document the impact of Paltus' attain on patient's quality of life.

Dana Pizzuti: The positive feedback we have received so far indicates that our patient-focused approach can help us develop better therapies that make a meaningful difference to patients.

Adam Mellman: The positive feedback we have received so far indicates that our patient focused approach can help us develop better therapies that make a meaningful difference to patients.

Jim Hazard: I'll now hand the call over to Jim to review commercial readiness strategy and current progress.

Adam Mellman: I'll now hand the call over to Jim to review commercial readiness strategy and current progress.

Jim Hazard: Thank you, Dana. For many years, Crinetics has been a committed member of the endocrinology community. We've participated in many medical conferences and learn from countless listening sessions with both patients and healthcare providers alike.

James Hassard: For many years, Crinetics has been a committed member of the endocrinology community. We've participated in many medical conferences and learned from countless listening sessions with both patients and health care providers alike. We're now on the verge of filing the Peltucetine NDA, an opportunity to establish a new standard of care in the treatment of acromegaly for patients, healthcare practitioners, and payers. Acromegaly is the first indication for peltucida.

Jim Hazard: Thank you, Dana.

Jim Hazard: for many years, Krenatics has been a committed member of the Endocrinology Community.

Jim Hazard: We've participated in many medical conferences and learn from countless listening sessions with both patients and healthcare providers alike.

Jim Hazard: We're now in the verge of filing the Paltusatine NDA, an opportunity to establish a new standard of care in the treatment of acromegaly for patients, healthcare practitioners, and payers. Acromegaly is the first indication for Paltusatine. Our launch preparation activities are laying the foundation of a fully integrated organization that can be leveraged for future indications, including carcinoid syndrome, as well as other drug candidates in our pipeline.

Jim Hazard: We're now in the verge of filing the Peltucetine NDA, an opportunity to establish a new standard of care in the treatment of acromagalline, for patients, healthcare practitioners and payers.

James Hassard: Our launch preparation activities are laying the foundation of a fully integrated organization that can be leveraged for future indications, including carcinoid syndrome, as well as other drug candidates in our pipeline. Our overarching strategy is to disrupt the established acromegaly marketplace, which has not seen any new molecules in over a decade. We are bringing a clinically differentiated, once daily oral medication to market with our commercial infrastructure and differentiated support services. Our commercial strategy is guided by three underlying pillars.

Jim Hazard: Acromegaly is the first indication for peltucetine.

Adam Mellman: Our launch preparation activities are laying the foundation of a fully integrated organization that can be leveraged for future indications, including car snide syndrome, as well as other drug candidates in our pipeline.

Jim Hazard: Our overarching strategy is to disrupt the established acromegaly marketplace, which has not seen any new molecules in over a decade. We are bringing a clinically differentiated, once daily, oral medication to market, with our commercial infrastructure and differentiated support services.

Adam Mellman: Our overarching strategy is to disrupt the established acromegaly marketplace.

Adam Mellman: which has not seen any new molecules in over a decade. We are bringing a clinically differentiated, once daily, oral medication to market with our commercial infrastructure and differentiated support services.

Jim Hazard: Our commercial strategy is guided by three underlying pillars. First, extending Crinetics' partnership with healthcare practitioners; second, empowering patients; and third, streamlining access to therapy. The first pillar is extending our partnership with the endocrinology community. We will be launching into a concentrated prescriber base of approximately 200 healthcare practitioners who are responsible for the vast majority of prescriptions. These providers can be reached with a small sales force of approximately 25 to 30 sales representatives in conjunction with other activities across the organization, including medical affairs. As we deepen our relationships with prescribers, we are building awareness of the patient experience and burden associated with the current standard of care.

Adam Mellman: Our commercial strategy is guided by three underlying pillars.

James Hassard: First, extending Crinetics' partnership with health care practitioners. Second, empowering patients. And third, streamlining access to therapy.

Adam Mellman: First Extending Critics Partnership with Healthcare Practitioners, Second Empowering Patients, and Third Stringlining Access to Therapy.

James Hassard: The first pillar is extending our partnership with the endocrinology community. We will be launching into a concentrated prescriber base of approximately 200 healthcare practitioners, who are responsible for the vast majority of prescriptions. These providers can be reached with a small sales force of approximately 25 to 30 sales representatives, in conjunction with other activities across the organization, including medical affairs.

Please stand by. Your program is about to begin. If you need assistance on today's program, please press star zero.

Adam Mellman: The first pillar is extending our partnership with the endocrinology community. We will be launching into a concentrated prescriber base of approximately 200 healthcare practitioners who are responsible for the vast majority of prescriptions.

Unknown Executive: Good day everyone and welcome to the Crinetics Pharmaceuticals second quarter, 2024 earnings conference call. At this time all participants are any listed in only mode. Later you will have the opportunity to ask questions during the question and answer session. You may register to ask a question at any time by pressing the star in one on your telephone keypad. You may withdraw yourself from the queue by pressing star two. Please note this call may be recorded. I'll be standing by. Should you need any assistance?

Adam Mellman: These providers can be reached with a small sales force of approximately 25 to 30 sales representatives, in conjunction with other activities across the organization, including medical affairs.

James Hassard: As we deepen our relationships with prescribers, we are building awareness of the patient experience and burden associated with the current standard of care. We've conducted multiple lines of market research, and one common theme is a disconnect between what physicians perceive and what their patients actually experience. For example, we found that endocrinologists believe two-thirds of their acromegaly patients on pharmacotherapy are well-controlled biochemically and symptomatically. However, in our patient surveys, we've found that 79% of acromegaly patients report breakthrough symptoms, which are symptoms that often reemerge toward the end of their monthly treatment cycle.

Adam Mellman: As we deepen our relationship with prescribers, we are building awareness of the patient experience in burden associated with the current standard of care.

Jim Hazard: We have conducted multiple lines of market research, and one common theme is a disconnect between what physicians perceive and what their patients actually experience. For example, we found that endocrinologists believe two-thirds of their acromegaly patients on pharmacotherapy are well-controlled biochemically and symptomatically. However, in our patient's surveys, we found that 79% of acromegaly patients report breakthrough symptoms. These are symptoms that often reemerge toward the end of their monthly treatment cycle. Patients have indicated that the treatment burden and breakthrough symptoms can be detrimental to their lives, but patients may not mention this during their physician appointments. So, if doctors aren't asking and patients aren't volunteering this information, the disconnect is not being addressed.

Adam Mellman: We've conducted multiple lines of market research, and one common theme is a disconnect between what physicians perceive and what their patients actually experience.

Gaia III DeWalker: It is not my pleasure to turn the program over to Gaia III DeWalker. Thank you, operator. Hello everyone and welcome to Crinetics earning call. Joining me today are Dr. Scott Strothers, founder and chief executive officer. Dr. Dana Pizzuti, chief medical and development officer, Jim Hazard, chief commercial officer, and Marc Wilson, chief financial officer. Also joining us for the Q&A portion of the call is Dr. Alan Krasner, chief under chronologist. Approximately announcing the second quarter, 2024 financial results was issued today and is also available on our corporate website.

Adam Mellman: For example,

Adam Mellman: We found that endocrinologists believe two-thirds of their acromegaly patients on pharmacotherapy are well-controlled biochemically and symptomatically. However, in our patient surveys, we found that 79% of acromegaly patients report breakthrough symptoms.

Adam Mellman: Now these are symptoms that often reemerge toward the end of their monthly treatment cycle.

James Hassard: Patients have indicated that the treatment burden and breakthrough symptoms can be detrimental to their lives, but patients may not mention this during their physician appointment. So, if doctors aren't asking and patients aren't volunteering this information, the disconnect is not being addressed. Healthcare practitioners are always seeking the best treatment for their patients, and today they don't always have complete visibility into their patients' experiences. We at Crinetics are dedicated to providing an option that addresses the limitations of the current standard of care.

Adam Mellman: Patients have indicated that the treatment burden and breakthrough symptoms can be detrimental to their lives, but patients may not mention this during their physician appointments.

Gaia III DeWalker: We will be using slides for today's presentation, which can be viewed on the investor relations section of the Crinetics website. As a reminder, we'll be making forward-looking statements and invite you to learn more about the risks and uncertainties associated with these statements as disclosed in our SEC filing. Such forward-looking statements are not a guarantee of performance and the company's actual results could differ materially from those stated or implied in substatements due to risks and uncertainties associated with the company's business.

Speaker Change: So, if doctors aren't asking and patients aren't volunteering this information, the disconnect is not being addressed.

Jim Hazard: Healthcare practitioners are always seeking the best treatment for their patients, and today they don't always have complete visibility into their patient's experience.

Speaker Change: Healthcare practitioners are always seeking the best treatment for their patients. And today, they don't always have complete visibility into their patient's experience.

Jim Hazard: We at Crinetics are dedicated to providing an option that addresses the limitations of the current standard of care. We want to bridge the frequent discount and connect in dialogue and help healthcare practitioners become more aware of the patient experience, including the pain and challenges associated with intramuscular and deep subcutaneous injections, and the breakthrough symptoms that can occur at the end of the somatostatin receptor ligand injection cycle. We believe Peltucetine may provide a better treatment option for patients, as it was designed to address the limitations of today's standard of care. Our commercial team has recently launched acromeglytruth.com, our disease awareness campaign for endocrinologists treating patients with acromegaly, which you can see on slide 7.

Crinetics: We at Crinetics are dedicated to providing an option that addresses the limitations of the current standard of care.

Gaia III DeWalker: These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release, the company's other news releases and the Crinetics SEC filing, including its annual report on form 10K. I would also like to specify that the content of this conference call contains time-sensitive information that's accurate only as the date of this live broadcast August 8, 2024. Crinetics takes your obligation to revise or update any forward-looking statements to flip events or circumstances after the date of this conference call.

James Hassard: We want to bridge the frequent disconnect in dialogue and help healthcare practitioners become more aware of the patient experience, including the pain and challenges associated with intramuscular and deep subcutaneous injections and the breakthrough symptoms that can occur at the end of the somatostatin receptor ligand injection cycle.

Adam Mellman: We want to bridge the frequent disconnect in dialogue and help healthcare practitioners become more aware of the patient experience.

Adam Mellman: including the pain and challenges associated with intramuscular and deep subcutaneous injections and the breakthrough symptoms that can occur at the end of the somatostatin receptor ligand injection cycle.

James Hassard: We believe Peltucetine may provide a better treatment option for patients as it was designed to address the limitations of today's standard of care. Our commercial team has recently launched acromegalytruth.com, our disease awareness campaign for endocrinologists treating patients with acromegaly, which you can see on slide 7. More than 1,500 providers have already interacted with this site so far. acromegalytruth.

Adam Mellman: We believe Peltucetine may provide a better treatment option for patients as it was designed to address the limitations of today's standard of care.

Gaia III DeWalker: Without, I'll hand the call over to Scott. Thank you, Guy Astrid.

Scott Strothers: Good afternoon, everyone, and thank you for joining us on our second quarter 2024 results call. I'll begin by spending a few moments summarizing our recent accomplishments.

Speaker Change: Our commercial team has recently launched AccromagelyTruth.com, our disease awareness campaign for endocrinologists treating patients with Accromagely, which you can see on slide 7.

Scott Strothers: Then, I will hand the call over to Dr. Dana Pizuti, our chief medical and development officer who will provide a regulatory update.

Jim Hazard: More than 1,500 providers have already interacted with this site so far. Acromeglytruth.com includes perspectives from patients on injectable SRLs, including injection site reactions and GI side effects, breakthrough symptoms, and emotional impact of treatment. In addition, we believe that positive data from the acromegaly symptom diary, which was one of the secondary endpoints used in the Pathfinder Phase 3 program, will help healthcare practitioners understand the clinical benefits of Peltucetine, which go well beyond biochemical control. In fact, we have already shared some of this data from the acromegaly symptom diary at Endo this past June. We hope this data will help physicians understand the potential transformative impact of Peltucetine for their patients.

Speaker Change: More than 1500 providers have already interacted with this site so far.

Jim Hazard: Jim Hazard, our chief commercial officer, will share our plans to bring our lead candidate, Peltus, team to patients.

Speaker Change: AcromegalyTruth.com includes perspectives from patients on injectable SRLs, including injection site reactions,

Scott Strothers: Mark Wilson, our chief financial officer, will wrap up with a thrilling financial update. The second quarter of 2024 was extremely productive for Crinetics. The Endocrine Society Annual Meeting in June proved to be an impactful meeting for us. We were thrilled to share highly encouraging initial results from the ongoing phase two studies of our second development candidate, Atumelna, in both congenital adrenal hyperplasia and cushions. Disease. These unprecedented data were very well received by the under-conology community.

James Hassard: Side Effects, Breakthrough Symptoms, and Emotional Impact of Treatment. In addition, we believe that positive data from the Acromegaly Symptom Diary, which was one of the secondary endpoints used in the Pathfinder Phase 3 program, will help healthcare practitioners understand the clinical benefits of peltucetine, which go well beyond biochemical control. In fact, we have already shared some of this data from the Acromegaly Symptom Diary at Endo this past June. We hope this data will help physicians understand the potential transformative impact of peltucetine for their patients. We already have strong relationships with academic key opinion leaders in pituitary treatment centers.

Speaker Change: GI Side Effects, Breakthrough Symptoms, and Emotional Impact of Treatment.

Speaker Change: In addition, we believe that positive data from the Acromegaly Symptom Diary, which was one of the secondary endpoints used in the Pathfinder Phase III program, will help healthcare practitioners understand the clinical benefits of peltucetine, which go well beyond biochemical control.

Speaker Change: In fact, we have already shared some of this data from the Acromegaly Symptom Diary at Endo this past June . We hope this data will help physicians understand the potential transformative impact of peltucetine for their patients.

Scott Strothers: This reinforced our already strong confidence in the potential of ATEML-NAT to be a best in class and first in class agent in both indications. Cations need better therapeutic options and we are committed to realizing ATEML-NAT's full potential as a revolutionary new treatment paradigm for people suffering from CH and Cushing's disease. Crinetics team is working hard to move development of ATEML-NAT for it in both indications and bring this potential therapy to people around the world.

Jim Hazard: We already have strong relationships with academic key opinion leaders in the pituitary treatment centers. As another example of our commercial execution, we are looking to expand our relationship with endocrinologists in the community setting. To that end, we've assembled an initial team of thought leader liaisons who are in the field, deepening our relationships with clinical endocrinologists who are managing patients day in and day out.

Speaker Change: We already have strong relationships with academic key opinion leaders in the pituitary treatment centers

James Hassard: As another example of our commercial execution, we are looking to expand our relationship with endocrinologists in the community setting. To that end, we've assembled an initial team of thought leader liaisons who are in the field deepening our relationships with clinical endocrinologists who are managing patients day in and day out. The second pillar of our commercial plan is empowering patients to ask for better care and improved control of their symptoms. We recognize the vital role patients play in advocating for their diagnosis, managing their disease, and seeking optimal treatment.

Speaker Change: As another example of our commercial execution, we're looking to expand a relationship with chronologist in the community setting.

Speaker Change: To that end, we've assembled an initial team of thought leader Lia Zons, who are in the field deepening our relationships with clinical endocrinologists who are managing patients day in and day out.

Jim Hazard: The second pillar of our commercial plan is empowering patients to ask for better care and improve control of their symptoms. We recognize the vital role patients play in advocating for their diagnosis, managing their disease, and seeking optimal treatment. To this end, we plan to launch next year an expanded disease awareness campaign targeted towards patients with acromegaly. The goal is to help patients realize that better control of their acromegaly symptoms and the lower treatment burden may be possible. Ultimately, we want to empower patients to ask their health care practitioner for Peltucetine once approved. As Dana mentioned, our patient advocacy team has been engaging with the acromegaly patient organizations since early in clinical development.

Scott Strothers: We also presented data from Paltusa Team's Pathfinder Phase 3 Acromegely Program at Endo. A new analysis from Pathfinder 1 highlights results, highlighted results from an exploratory analysis using patient-reported outcomes captured in the Acromegely Symptom Diary or ASD. These data showed that patients on monthly standard of care injections were defined as biochemically controlled, actually experienced variable variability in symptom control. In contrast, once daily Paltusa Team was associated with stable biochemical control and low rates of breakthrough symptoms. Dana and Jim will speak a more on our progress of bringing Paltusa Team patients but I'm incredibly excited about its potential to transform the future of Acromegely treatment and to find a new standard of care.

Speaker Change: The second pillar of our commercial plan is empowering patients to ask for better care and improve control of their symptoms.

Speaker Change: We recognize the vital role patients play in advocating for their diagnosis, managing their disease, and seeking optimal treatment.

James Hassard: To this end, we plan to launch next year an expanded disease awareness campaign targeted towards patients with acromegaly. The goal is to help patients realize that better control of their acromegaly symptoms and a lower treatment burden may be possible.

Speaker Change: To this end, we plan to launch next year and expand its disease awareness campaign targeted towards patients with acromagalli. The goal is to help patients realize that better control of their acromagalli symptoms and the lower treatment burden may be possible.

James Hassard: Ultimately, we want to empower patients to ask their healthcare practitioner for peltucetine once approved. As Dana mentioned, our patient advocacy team has been engaging with acromegaly patient organizations since early in clinical development. We are continuing to strengthen our relationship with the patient community to ensure that we are addressing the needs of patients. The third pillar of our commercial plan is to ensure optimal patient access to our best-in-class therapy. The national account team responsible for all payer interactions is in place and onboarded.

Speaker Change: Ultimately, we want to empower patients to ask their healthcare practitioner for Peltucetene once approved.

Speaker Change: As Dana mentioned, our patient advocacy team has been engaging with the Acromegaly patient organizations since early in clinical development. We are continuing to strengthen our relationship with the patient community to ensure we are addressing the needs of patients.

Jim Hazard: We are continuing to strengthen our relationship with the patient community to ensure we are addressing the needs of patients.

Scott Strothers: Overall, our 2024 plans remain on track. Our next steps this year include filing the Paltusa Team NDA for Acromegely, engaging with regulators to align on the initiation of a Phase 3 program in carcinoid syndrome, completing the Phase 2 studies of FMLNF and CAH and Cushing's and transitioning multiple new drug candidates from our discovery efforts into pre-clinical and IND-enabling development. Along these lines, we've continued to make meaningful progress on our early stage pipeline.

Jim Hazard: The third pillar of our commercial plan is to ensure optimal patient access to our best-in-class therapy. The national account team responsible for all payer interactions is in place and onboarded. We have had discussions with the top commercial and government payers covering the majority of lives in the country, and initial feedback from those payer advisory meetings has been encouraging. Patient Support Center to help streamline the prescribing, dispensing, and reimbursement process. This support center is being designed based on our ongoing market research and discussions with patients to develop best practices and close the gaps in the current reimbursement processes.

Speaker Change: The third pillar of our commercial plan is to ensure optimal patient access to our best-in-class therapy.

Speaker Change: The National Account Team responsible for all payer interactions is in place and onboarded.

James Hassard: We have had discussions with the top commercial and government payers covering the majority of lives in the country, and initial feedback from those payer advisory meetings has been encouraging. We are finalizing a highly differentiated patient support center to help streamline the prescribing, dispensing, and reimbursement processes. This support center is being designed based on our ongoing market research and discussions with patients to develop best practices and close the gaps in the current reimbursement processes.

Speaker Change: We have had discussions with the top commercial and government payers, covering the majority of lives in the country. And initial feedback from those payer advisory meetings has been encouraging.

Scott Strothers: First, we've identified a parathyroid hormone or PTH receptor antagonist development candidate for our hyperparathyroidism program. Pre-clinical data demonstrates that this candidate reduces both PTH and PTH-related protein-induced hypercalcemia in rodent models and it possesses a favorable drug-like profile.

Speaker Change: We are finalizing a highly differentiated patient support center to help streamline the prescribing, dispensing, and reimbursement process.

Speaker Change: This support center is being designed based on our ongoing market research and discussions with patients to develop best practices and close the gaps in the current reimbursement processes.

Scott Strothers: This profile is likely consistent with once per day dosing in humans. We've begun IND-enabling studies in anticipate filing an IND in 2025.

Jim Hazard: We have also finalized our distribution channel.

James Hassard: We have also finalized our distribution channel, and we look forward to sharing more details at our next earnings call. In addition to establishing the commercial foundation for a successful launch, our medical affairs team is engaging in robust scientific discussions throughout the medical community. We've hired Dr. Bob Cuddehy, an experienced endocrinologist who has dedicated much of his career to treating patients, including those with acromegaly, and has built and led medical affairs functions at other organizations such as Janssen, Sanofi, and Amgen.

Jim Hazard: We look forward to sharing more details at our next earnings call.

Speaker Change: We have also finalized our distribution channel. We look forward to sharing more details at our next earnings call.

Jim Hazard: In addition to establishing the commercial foundation for a successful launch, our medical affairs team is engaging in robust scientific discussions throughout the medical community. We've hired Dr. Bob Cuddy, an experienced endocrinologist who has dedicated much of his career to treating patients, including those with acromegaly, and has built and led medical affairs functions at other organizations such as Jensen, Santa Fe, and Amgen.

Scott Strothers: We've also selected an SST-3 agonist development candidate to explore a completely new mechanism for the treatment of autosomal dominant polyphonic kidney disease or ADPKD. ADPKD, excuse me, lost my place, ADPKD is one of the most common genetic diseases and affects over 140,000 people in the U.S. Pre-clinical data for this candidate are very promising and we are pursuing options to advance this program to clinical studies either with a partner or independently.

Speaker Change: In addition to establishing the commercial foundation for a successful launch, our medical affairs team is engaging in robust scientific discussions throughout the medical community.

Speaker Change: We've hired Dr. Bob Cuddehy, an experienced endocrinologist who has dedicated much of his career to treating patients, including those with acromegaly.

Speaker Change: and has built and led medical affairs functions at other organizations such as Johnson, Santa Fe, and Amgen.

Jim Hazard: In conclusion, chronetics continues our evolution to ensure that we are in the best position to execute our launch strategy following approval. The Paltucetine data that have been generated to date puts us in a unique position to demonstrate a highly differentiated clinical profile across multiple dimensions, including biochemical control, symptom control, tolerability, and the overall patient experience. We know what is important to patients, to the physicians who treat them, and to the health care system. And we believe in the value proposition of Paltucetine, which serves each of these constituencies well.

James Hassard: In conclusion, Crinetics continues to evolve to ensure that we are in the best position to execute our launch strategy following approval. The Peltucetine data that have been generated to date puts us in a unique position to demonstrate a highly differentiated clinical profile across multiple dimensions, including biochemical control, symptom control, tolerability, and the overall patient experience. We know what is important to patients, to the physicians who treat them, and to the healthcare system, and we believe in the value proposition of Peltucetine, which serves each of these constituencies well.

Speaker Change: In conclusion, Crinetics continues our evolution to ensure that we are in the best position to execute our launch strategy, following approval.

Scott Strothers: Our discovery programs for graze disease Discovery Program for Grace Disease including thyroid eye disease and obesity continue to make great progress and we look forward to announcing optimized candidates for these programs in the near future. As a reminder, our pipeline also includes novel molecules and technologies that are being developed by our partners. For example, several years ago, we developed a novel non peptide radiotherapy agnostic program that could be used in multiple oncology indications.

Speaker Change: The Peltucetine data that have been generated to date puts us in a unique position to demonstrate a highly differentiated clinical profile across multiple dimensions including biochemical control, symptom control, tolerability, and the overall patient experience.

Speaker Change: We know what is important to patients, to the physicians who treat them and to the healthcare system.

Speaker Change: And we believe in the value proposition of Peltucetine, which serves each of these constituencies well.

Scott Strothers: With this, we created a company around the technology called radionetics oncology and entered into a collaboration and license agreement with the company. Radionetics announced on July 1st that it entered into a strategic relationship with Eli Lillian company. Under the terms of the agreement, radionetics received $140 million upfront and lily obtained a warrant for the exclusive right to purchase radionetics for one billion. Chronetics currently owns approximately 25% of radionetics. If Lily were to exercise its right to purchase radionetics, Chronetics would receive its pro-reda share of the $1 billion purchase price.

Jim Hazard: Over the coming months leading up to the expected launch in 2025, we will continue to implement our commercial strategy and share updates along the way. I believe in the transformative potential of Paltucetine for patients with acromegaly, and I'm excited to be leading our commercial team to launch this therapy.

James Hassard: Over the coming months, leading up to the expected launch in 2025, we will continue to implement our commercial strategy and share updates along the way. I believe in the transformative potential of peltucetine for patients with acromegaly, and I'm excited to be leading our commercial team to launch this therapy. We are laying the foundation for a fully integrated pharmaceutical company that will be prepared for future peltucetine indications, as well as other products in the Crinetics pipeline. With that said, I will now hand it over to Marc to review the financials.

Speaker Change: Over the coming months, leading up to the expected launch in 2025, we will continue to implement our commercial strategy and share updates along the way.

Speaker Change: I believe in the transformative potential of teletucity and for patients with acromagalline. And I'm excited to be leading our commercial team to launch this therapy.

Jim Hazard: We are laying the foundation for a fully integrated pharmaceutical company that will be prepared for future Paltucetine indications, as well as other products in the chronetics pipeline.

Speaker Change: We are laying the foundation for a fully integrated pharmaceutical company that will be prepared for future Peltucetine indications, as well as other products in the Cranex pipeline.

Mark Wilson: With that, I will now hand it over to Mark to review the financials.

Scott Strothers: Chronetics is also entitled to single digital royalties and commercialization milestones for the three programs currently in development of radionetics. We believe this transaction is a great validation of the strength of our discovery platform and has the potential to generate non-divitive funding for kinetics in the future.

Speaker Change: With that, I will now hand it over to Marc to review the financials.

Mark Wilson: Thank you, Jim.

Marc Wilson: As Scott mentioned, I will be stepping down from my role as CFO at Crinetics for personal reasons. Crinetics is in very capable hands with its deep bench of leaders across the organization.

Mark Wilson: As Scott mentioned, I will be stepping down from my role as CFO at Chronetics for personal reasons. Chronetics is in very capable hands with its deep bench of leaders across the organization. I am proud of all the way of accomplished during my tenure, and I look forward to the company's continued success, and it evolves into a fully integrated endocrinology franchise.

Marc Wilson: Thank you, Jim.

Marc Wilson: As Scott mentioned, I will be stepping down from my role as CFO at Planetage for personal reasons.

Marc Wilson: Pronetics is in very capable hands with its deep bench of leaders across the organization.

Marc Wilson: I am proud of all we have accomplished during my tenure, and I look forward to the company's continued success as it evolves into a fully integrated endocrinology franchise. With that, I'll now review the second quarter financial results. Pranetics continues to be in a strong financial position, having ended the second order with approximately $863 million in cash in advance. Our solid financial foundation is projected to fund our current operating plan into 2021.

Scott Strothers: We also have a partnership with Wood, in which we license another one of our targeted Somatos Fountain molecules to extend the lifespan and health span of dogs. The company, the entire company is hard at work executing our strategy to help more patients with endocrine-related diseases and to build long-term value for kinetics shareholders.

Mark Wilson: With that, I will now return to review the second quarter financial results. Prinetics continues to be in a strong financial position, having ended the second quarter with approximately $863 million in cash and investments. Our solid financial foundation is projected to fund our current operating plan into 2020. This includes plans to commercialize Peltusatine for Acro-Megley, the initiation of multiple later stage clinical trials in additional indications with Peltusatine and Anti-Mailment, as well as continued investment in our pipeline. With respect to the second quarter financial results, research and development expenses were $58.3 million for the quarter end of June 30, 2024, compared to $40.6 million for the same period in 2023.

Marc Wilson: This includes plans to commercialize paltucetine for acromegaly, the initiation of multiple later stage clinical trials, and additional indications with paltucetine and entomelanate, as well as continued investment in our pipeline. Research and development expenses were $58.3 million for the quarter ended June 30, 2024, compared to $40.6 million for the same period in 2023. The increase was primarily attributable to higher personnel costs and manufacturing and development activities.

Scott Strothers: Lastly, as you may have seen in our press release, Mark, our chief financial officer, will be leaving the company for personal reasons. The Chronetics executive team in board are grateful for Mark's contributions to the company, as he has been an invaluable member of the Chronetics team since before the IPO. His leadership was instrumental in the success of all our public market activities, which we have put Chronetics on a strong financial footing. We've initiated a search for a successor and Mark will remain in his current position until a successor is onboarded to ensure a seamless transition.

Dana Pizzuti: With that, I'll hand it over to Dr. Dana Favuti to discuss our clinical and regulatory progress in more detail. Thank you. Thank you, Scott.

Mark Wilson: The increase was primarily attributable to higher personnel costs and manufacturing and development activities, both of which were driven by the advancement of our clinical programs and the expansion of our pre-clinical portfolio. For the quarter end of June 30, 2024, general and administrative expenses were $24.8 million compared to $13.3 million for the same period in 2023. The change was primarily due to an increase in personnel costs and an increase in outside services as we continue to build the infrastructure to support our growing pipeline. Net loss for the quarter end of June 30, 2024, was $74.1 million compared to a net loss of $51 million for the same period in 2023.

Speaker Change: The increase was primarily attributable to higher personnel cost and manufacturing and development activities.

Dana Pizzuti: I'll start with our lead candidate, Paltuza team. As Scott just mentioned, we remain on track to submit our NTA for Paltuza team in its first indication acromegally this year. As we have discussed, the phase three pathfinder program was designed to evaluate the safety and efficacy of Paltuza team for the treatment of a broad spectrum of patients with acromegally. Based on the success of both phase three pathfinder studies, we intend to seek approval for all patients, including those switching from the standard of care injected SRLs to Paltuza team, as studied in pathfinder one, and those who are not currently treated as studied in pathfinder two.

Marc Wilson: Both of which were driven by the advancement of our clinical programs and the expansion of our preclinical portfolio. For the quarter ended June 30th, 2024, general and administrative expenses were $24.8 million compared to $13.3 million for the same period in 2020. The change was primarily due to an increase in personnel costs and an increase in outside services as we continue to build the infrastructure to support our growing pipeline.

Speaker Change: Most of which were driven by the advancement of our clinical programs and the expansion of our preclinical portfolio.

Speaker Change: For the quarter ended June 32020 for general and administrative expenses were $24 8 million compared to $13 3 million for the same period in 2023.

Marc Wilson: The change was primarily due to an increase in personnel costs and an increase in outside services as we continue to build the infrastructure to support our growing pipeline.

Marc Wilson: The net loss for the quarter ended June 30, 2024 was $74.1 million, compared to a net loss of $51 million for the same period in 2023. Revenues were $0.4 million for the quarter ended June 30, compared to $1 million for the same period in 2023. Revenues during the current year's quarter were derived from the Paltusa team licensing arrangement with our Japanese partner, SKK. Net cash used for operating activities for the quarter ended June 30th, 2024, was $45.6 million. We expect our cash burn to be approximately $50 to $60 million per quarter for the remainder of 2024. I will now hand it back to Scott for closing remarks before we begin Q&A.

Marc Wilson: Net loss for the quarter ended June 32024 was $74 1 million compared to a net loss of $51 million for the same period in 2023.

Mark Wilson: The revenues were $0.4 million for the quarter end of June 30, compared to $1 million for the same period in 2023. Revenues during the current year's quarter were derived from the Peltusatine licensing arrangement with our Japanese partner, SKK. Net cash used for operating activities for the quarter end of June 30, 2024, was $45.6 million. We expect our cash burn to be approximately $50 to $60 million per quarter for the remainder of 2024.

Speaker Change: Our revenues were <unk> 4 million for the quarter ended June 30, compared to $1 million for the same period in 2023.

Dana Pizzuti: In parallel with our phase 3 program, we have laid the foundations to streamline and accelerate the NDA filing. We have held two productive pre-NDA interactions with the FDA to align on clinical, non-clinical, CMC, and quality topics. The FDA confirmed that our proposed package supports admission for both the maintenance of aqua-megely. This robust package includes data from our two Pathfinder Phase 3 studies, as well as dose response analyses, data from our long-term safety studies, and patient outcomes from the aqua-megely symptom diary, which showed significant improvements in patient-reported symptoms in both of our studies.

Marc Wilson: Revenues during the current year's quarter were derived from the <unk> licensing arrangement with our Japanese partner S. K K.

Speaker Change: Net cash used for operating activities for the quarter ended June 32024.

Speaker Change: That was $45 6 million.

Marc Wilson: We expect our cash burn to be approximately approximately $50 million to $60 million per quarter for the remainder of 2024.

Mark Wilson: I will now hand it back to Scott for closing remarks before we begin Q&A.

Speaker Change: I will now hand, it back to Scott for closing remarks, before we begin the Q&A.

Scott Strothers: Thank you, Mark. Looking to the rest of 2024 and 2025, we'll continue to build on the strong progress today. We look forward to upcoming clinical and regulatory milestones from Peltusatine and Atumelnet and continued advancement of our deep pipeline of emerging candidates.

Scott: Thank you Mark.

Scott Struthers: Looking to the rest of 2024 and 2025, we'll continue to build on the strong progress to date. We look forward to upcoming clinical and regulatory milestones for Paltucetine and Atumelanet and continued advancement of our deep pipeline of emerging candidates. Crinetics continues to be well-positioned to become the premier, fully integrated, endocrine-focused pharmaceutical company.

Scott: Looking to the rest of 2024 and 25 and we will continue to build on the strong progress today, we look forward to upcoming clinical and regulatory milestones from <unk> and <unk> and continued advancement of our deep pipeline of emerging candidates.

Dana Pizzuti: We look forward to updating you as we continue towards the NDA file. In addition, we are diligently conducting healthy genomics and outcome studies to further demonstrate the value proposition of Paltuza team in aqua-megely. This work supports the commercial team's efforts as they engage with payers, physicians, and patients.

Scott Strothers: Chronoetics continues to be well positioned to become the premier, fully integrated, endocrine-focused pharmaceutical company. Thank you all for your attention.

Speaker Change: <unk> continues to be well positioned to become the premier fully integrated endocrine focused pharmaceutical company.

Scott Struthers: Thank you all for your attention. Operator, we're ready to take questions. For folks on the call, we'd appreciate it if you could limit yourself to one question. We have a lot of analysts on the call. I want to ensure that we can provide each of you with a thoughtful response. Thank you, everybody. And at this time, if you would like to ask a question, please press star one now on your telephone keypad to withdraw yourself from the queue. You may.

Scott: Thank you all for your attention.

Unknown Executive: Operator, we're ready to take questions. For folks on the call, we'd appreciate it if you could limit yourself to one question. We have a lot of analysts on the call. I want to ensure that we can provide each of you with a thoughtful response. Thank you very much.

Speaker Change: Operator, we're ready to take questions for folks on the call. We'd appreciate it if you could limit yourself to one question. We have a lot of analysts on the call I want to ensure that we can provide each of you with a thoughtful response.

Dana Pizzuti: We are also making progress in Paltuza team's second indication, carcinoid syndrome. As previously reported, our Phase 2 study showed highly statistically significant results demonstrating the potential of Paltuza team to treat people living with carcinoid syndrome. Importantly, the patients who elected to participate in the ongoing open-label extension continue to benefit from Paltuza team. Building on this success, we are preparing to discuss the Phase 2 results with the FDA and align on the design of a Phase 3 protocol. We expect to initiate the Phase 3 trial by the end of 2024.

Speaker Change: Thank you for that okay.

Unknown Executive: And at this time, if you would like to ask a question, please press star one now on your telephone keypad. To withdraw yourself from the queue, you may press star two.

Operator: And at this time, if you would like to ask a question, please press star one on your telephone keypad to withdraw yourself from the queue. Then, you may press star two.

Speaker Change: And at this time, if you would like to ask a question. Please press star one now on your telephone keypad to withdraw yourself from the queue you May press star two.

Jessica Fye: We'll take our first question from Jessica Fy of JP Morgan.

Operator: We'll take our first question from Jessica Fye of J.P. Morgan.

Speaker Change: We will take our question from first question from Jessica Fye of Jpmorgan.

Jessica Fye: Hey guys, good afternoon. Thanks for taking my question and Mark. It's been great working with you over the years.

Jessica Fye: Hey, guys. Good afternoon. Thanks for taking my question and Mark it's been great working with you over the years.

Alan Krasner: I was wondering how we should think about what additional insights we could expect to gain from the phase two updates in CAH and Cushing's coming later this year, and what venue or venues we should look for those at.

Jessica Fye: I was wondering how we should think about what additional insights we could expect to gain from the phase two updates in CAH and Cushings coming later this year.

Dana Pizzuti: Turning now to Adam Melment, we are excited about the progress and potential of Adam Melment in both CAH and Cushing's Disease. As Scott mentioned, the initial results from the open-label Phase 2 studies, which were featured at Endo, have exceeded our expectations. The three cohorts evaluating different doses of Adam Melment in the CAH Phase 2 study are now fully enrolled. We anticipate additional data will be available this year, and we are excited to advance this program. We also expect to share additional data from the ongoing study in ACTH dependent Cushing's Central later this year.

Speaker Change: Many of our venues we should look for those at.

Alan Krasner: Thank you, Jeff. I'll hand that over to Alan to give you a brief overview.

Alan Krasner: Thank you, Jess. Let me hand that over to Alan to give you a brief.

Speaker Change: Thank you, Jeff let me hand that over to Allen to give you a brief.

Alan Krasner: Yeah, you know, hopefully, we will have final or top-line results in CAH and Cushing's disease, and we will be able to sort of continue to support the messages, I believe, that we have already communicated at the Endocrine Society, meaning that this appears to be a uniquely effective agent in these disease states in terms of biomarker response. I think, you know, with higher sample sizes, we'll have a greater variety, a greater number of patients evaluated, and we'll have, most importantly, probably from the regulatory standpoint, a dose-response relationship fully described. And I think that's what will trigger, that's the information we need to really fully design our Phase 3 program and go forward and develop. Yeah, and maybe as a quick reminder.

Alan Krasner: Yeah, you know, we will have finals or top line results in CAH and Cushing's disease, hopefully, and we will be able to sort of continue to support the messages, I believe, that we have already communicated as the Endocrine Society, meaning that this appears to be a uniquely effective by agents in these disease states that in terms of biomarker responses, I think, you know, with higher sample sizes will have a greater variety, a greater number of patients evaluated and will have, most importantly, probably from the regulatory standpoint, the dose response really to the relationship fully described, and I think that's what will trigger that's the information you need to really fully design our case three program and go forward in development.

Speaker Change: Yes.

Allen: We will have.

Allen: Final top line results in.

Allen: CAH in Cushings disease hopefully.

Speaker Change: We will be able to sort of continue to.

Speaker Change: Support.

Speaker Change: Messages I believe that we have already communicated at the endocrine society in EMEA. This appears to be a uniquely effective by agent in states that in terms of biomarker responses.

Speaker Change: Thank you.

Speaker Change: With higher sample sizes will have a greater.

Dana Pizzuti: Prinetics is fundamentally committed to placing patients at the forefront of everything we do. This patient-centric approach is deeply ingrained in the development activities for each of the programs in our pipeline. We actively seek patient input throughout the drug development process. We've gained valuable insights by sharing data with patients, particularly from our ACRMEGALY program. These insights validate our commitment to developing treatments that improve patients' quality of life, such as offering convenient dosing regimens.

Speaker Change: Variety a greater number of patients to evaluate this and we'll have most importantly, probably from a regulatory standpoint, the dose response relationship.

Speaker Change: Fully described and I think thats, what will trigger testing information, we need to really fully design our phase III program Man go forward in development.

Alan Krasner: Yeah, and maybe as a quick reminder to those not as close to it as us that we now have the 40, 80, and 120 milligram cohorts enrolled, and the data from those groups will be available later this year. Thank you.

Unknown Executive: Yeah, and maybe as a quick reminder to those not as close to it as we are, that we now have the 40, 80, and 120 milligram cohorts enrolled, and the data from those groups will be available later this year.

Speaker Change: Yes, and maybe as a quick reminder, to those not as close to it as us.

Speaker Change: We now have 48 and $1 20 milligram cohorts.

Speaker Change: Enrolled and the data from those groups will be available later this year.

Dana Pizzuti: We have also routinely partnered with patient advocacy groups to obtain patient input on clinical trial design. Patients are enthusiastic about the potential of Paltusateen, recognizing that it not only delivers the desired biochemical control, but can also improve the symptom of the burden associated with their conditions. We invested considerable effort to develop the acromegaly symptom diary and are supporting that with psychometric analyses to help document the impact of Paltusatine on patient's quality of life. The positive feedback we have received so far indicates that our patient-focused approach can help us develop better therapies that make a meaningful difference to patients.

Speaker Change: Thank you.

Yasmeen Rahimi: We'll take our next question from Yasmeen Rahimi of Piper Sandler.

Operator: We'll take our next question from Yasmeen Rahimi of Piper Sandler.

Speaker Change: We will take our next question from Yasmin Rahimi of Piper Sandler.

Yasmeen Rahimi: Marc, we're going to greatly miss you. It's been a real pleasure working with you. You've done a tremendous job. So we will definitely miss you and hope the search continues for a little longer so we can continue working with you. Wanted to ask just a question on that.

Speaker Change: Okay.

Yasmeen Rahimi: Mark, we're going to greatly miss you. It's been really a pleasure working with you, and we have done a tremendous job. So we will definitely miss you and hope the search continues for a little longer so we can continue working with you.

Speaker Change: Mark we're going to greatly Miss you, it's been really a pleasure working with you already have done a tremendous job.

Speaker Change: We will definitely Miss John Hall.

Speaker Change: Search continues for a little longer so we can continue working with you.

Yasmeen Rahimi: I wanted to ask just a question on carcinoid.

Yasmin Rahimi: Wanted to ask just a question on carcinoid, if you could provide some color around engagement with the agency where are you in terms of the sign off.

Yasmeen Rahimi: If you could provide some color around engagement with the agency, where are you in terms of the sign-off?

Alan Krasner: And what sort of left to do to kick off the registration study, and I'll jump back into the queue. Yeah. Thanks, Danny.

Yasmin Rahimi: And what's sort of left to do to kickoff the Registrational study and I'll jump back into the queue.

Dana Pizzuti: Thanks guys. Dana, you want to handle that one?

Jim Hazard: I'll now hand the call over to Jim to review commercial readiness strategy and current progress. Thank you, Dana. For many years, Crinetics has been a committed member of the endocrinology community. We've participated in many medical conferences and learn from countless listening sessions with both patients and healthcare providers alike. We're now in the verge of filing the Paltusatine NDA, an opportunity to establish a new standard of care in the treatment of acromegaly for patients, healthcare practitioners, and payers.

Danny: Thanks, guys Danny.

Alan Krasner: You want to handle that one? Well, yeah, we've just completed all the analyses that we needed to do and are essentially ready to start the process of engaging with them, so it shouldn't take too long to get that squared away. As we mentioned, we're expecting to get the trial up and running by the end of the year.

Speaker Change: Danny you want to handle that one well yeah. We've just completed all the analysis that we needed to do.

Speaker Change: And are you now.

Speaker Change: Essentially.

Danny: Ready to.

Danny: Start the process of engaging with them. So it shouldn't take too long to get that squared away.

Dana Pizzuti: Well, yeah, we've just completed all the analyses that we needed to do and are, you know, essentially ready to, you know, start the process of engaging with them. So it shouldn't take too long to get that squared away. As we mentioned, we're expecting to get the trial up and running by the end of the year. So, you know, we have not yet completed the discussions with them. So, you know, we're sort of actively involved. We'll take our next question from Jeff Hung of Morgan Stanley. Thanks for taking my question and best wishes.

Speaker Change: We mentioned, we're expecting to get the trial up and running by the end of the year. So.

Alan Krasner: So, you know, we have not, you know, yet completed the discussions with them. So, you know, we're sort of actively involved.

Yasmin Rahimi: We have not.

Yasmin Rahimi: You know.

Speaker Change: Yes.

Speaker Change: <unk> the discussions with them so.

Jim Hazard: Acromegaly is the first indication for Paltusatine. Our launch preparation activities are laying the foundation of a fully integrated organization that can be leveraged for future indications, including carcinoid syndrome, as well as other drug candidates in our pipeline. Our overarching strategy is to disrupt the established acromegaly marketplace, which has not seen any new molecules in over a decade. We are bringing a clinically differentiated, once daily, oral medication to market, with our commercial infrastructure and differentiated support services.

Yasmin Rahimi: We are actively.

Yasmin Rahimi: Actively involved.

Jeff Hung: We'll take our next question from Jeff Hound of Morgan Stanley.

Operator: We'll take our next question from Jeff Hung of Morgan Stanley.

Speaker Change: We'll take our next question from Jeff Hung of Morgan Stanley.

Jeff Hung: Thanks for taking my question, and best wishes to Mark. You mentioned that you may advance your ADPKD program with a partner independently. What would be the deciding factors for Connection to go with one strategy versus the other?

Jeff Hung: Thanks for taking my question and best wishes to Mark <unk>.

Speaker Change: And that you may advance or 80, PK D program with a partner independently what would be the deciding factors for connection to go with one strategy versus the other and is that the only is that only relevant to this program are there specific early stage programs, but you would not be opening open to partnering.

Jeff Hung: Is that only relevant to this program, or are there specific early stage programs that you would not be open to partnering?

Scott Strothers: Thanks. Well, so there's a couple considerations. Thanks for the question, Jeff. A couple considerations. One is.

Unknown Executive: Well, so there are a couple considerations. Thanks for the question, Jeff.

Jeff Hung: Well.

Jeff Hung: So theres a couple of considerations. Thanks for the question Jeff.

Unknown Executive: A couple considerations. One is, you know, we've built a remarkably strong team in the endocrinology area, and we would need to start building out our kidney capabilities, our nephrology capabilities in order to do justice to this program. That being said, I think that's quite a reasonable thing for us to do. As a reminder, the polycystic kidney program and the PTH antagonist program both address the

Jim Hazard: Our commercial strategy is guided by three underlying pillars. First, extending Crinetics' partnership with healthcare practitioners, second, empowering patients, and third, streamlining access to therapy. The first pillar is extending our partnership with the endocrinology community. We will be launching into a concentrated prescriber base of approximately 200 healthcare practitioners who are responsible for the vast majority of prescriptions. These providers can be reached with a small sales force of approximately 25 to 30 sales representatives in conjunction with other activities across the organization, including medical affairs.

Jeff Hung: A couple of considerations one has.

Scott Strothers: You know, we've built a remarkably strong team in the under-cannology area, and we would need to start building out our kidney capabilities, our nephrology capabilities in order to do justice for this program. That being said, I think that's quite a reasonable thing for us to do as a reminder of the polycystic kidney program and the PTH antagonist program; both address nephrology populations. So there would be some synergy there. On the other hand, there may be groups out there that are further advanced in us in the field and could do better justice to this program more rapidly.

Jeff Hung: We've built a remarkably strong team in the endocrinology area.

Jeff Hung: And.

Speaker Change: We would need to start building out our kidney capabilities, our nephrology capabilities in order to do Justice for this program.

Jeff Hung: That being said I think that's quite a reasonable thing for us to do.

Jeff Hung: As a reminder, the polycystic kidney program and the PTH and tagging. This program both address nephrology populations.

Unknown Executive: So there would be some synergy there. On the other hand, there may be groups out there that are further advanced than us in the field and could do better justice to this program more rapidly. And I'll also just say that, given the productivity of our discovery group and the depth of our pipeline, I want to make sure that, from an internal perspective, we can grow adequately to give each program its due resources and attention. And so the growth of the company is a factor as well.

Jeff Hung: So there would be some synergies there on the other hand, there may be groups out there that are further advanced in us in the field and could do better justice to this program more rapidly.

Jim Hazard: As we deepen our relationships with prescribers, we are building awareness of the patient experience and burden associated with the current standard of care. We have conducted multiple lines of market research, and one common theme is a disconnect between what physicians perceive and what their patients actually experience. For example, we found that endocrinologists believe two-thirds of their acromegaly patients on pharmacotherapy are well-controlled biochemically and symptomatically. However, in our patient's surveys, we found that 79% of acromegaly patients report breakthrough symptoms.

Scott Strothers: And I'll also just say that, you know, given the productivity of our discovery group and the depth of our pipeline, I want to make sure that, from an internal perspective, we can grow adequately to give each program its due resources and attention. And so that growth of the company is a factor as well, and a very fortunate position to be able to have to make choices like this. Right, thank you.

Jeff Hung: And I'll also just say that.

Jeff Hung: Given the productivity of our discovery group and the depth of our pipeline I want to make sure that permanent internal perspective, we can grow adequately too.

Jeff Hung: Give each program, it's due resources and attention.

Jeff Hung: And so that growth of the company as a factor as well in a very fortunate position to be able to have.

Unknown Executive: We're in a very fortunate position to be able to have to make choices like this. Great. Thank you. We'll take our next question from Dennis Ding.

Speaker Change: You have to make choices like this.

Speaker Change: Great. Thank you.

Jim Hazard: These are symptoms that often reemerge toward the end of their monthly treatment cycle. Patients have indicated that the treatment burden and breakthrough symptoms can be detrimental to their lives, but patients may not mention this during their physician appointments. So, if doctors aren't asking and patients aren't volunteering this information, the disconnect is not being addressed. Healthcare practitioners are always seeking the best treatment for their patients, and today they don't always have complete visibility into their patient's experience.

Dennis Dean: We'll take our next question from Dennis Dean of Jeffries. Hi, thanks for taking our questions. Maybe if I can ask one on Akram Negoli, curious how you're thinking about the pricing strategy. Once you guys eventually get approved next year, if you plan a price at a premium, give in your north.

Operator: We'll take our next question from Dennis Ding of Jeffries.

Speaker Change: We will take our next question from Dennis <unk> of Jefferies.

Dennis: Hi, Thanks for taking my questions, maybe if I can ask one on acromegaly curious how youre thinking about the pricing strategy once you.

Speaker Change: It depends if we get approved next year.

Speaker Change: Priced at a premium given your normal thank you so much.

Dennis Dean: Thank you so much. Thanks, Dennis.

Unknown Executive: Thanks, Dennis. I'll let Jim handle that one. Thanks, Dennis, you know, still too early to

Jim Hazard: Thanks, Tom I'll, let Jim handle that one.

Jim Hazard: I'll add Jim Handle Allen. Thanks, Dennis.

James Hassard: Thanks, Dennis. You know, still too early to talk about pricing. We are engaged with, as we mentioned, engaged with payers and sharing the value proposition, and again, there have been some encouraging conversations to date. But again, we just need to have a deeper look at a number of factors before we disclose pricing, probably next year.

Jim Hazard: You know, still too early to talk about pricing. We are engaged with, as we mentioned, we are engaged with payers and sharing the value proposition. And again, it has been some encouraging conversations to date. But again, we just need to have a deeper look at a number of factors before we disclose pricing, probably next year.

Jim Hazard: So it is still too early to.

Speaker Change: To.

Speaker Change: Talk about about pricing we are engaged with as we mentioned we are engaged with payers and sharing the value proposition.

Speaker Change: And again it has been some encouraging conversations to date.

Speaker Change: But again, we just need to have a deeper look.

Speaker Change: At a number of factors before we disclose pricing probably next year.

Jim Hazard: We at Crinetics are dedicated to providing an option that addresses the limitations of the current standard of care. We want to bridge the frequent discount and connect in dialogue and help healthcare practitioners become more aware of the patient experience, including the pain and challenges associated with intramuscular and deep subcutaneous injections, and the breakthrough symptoms that can occur at the end of the somatostatin receptor ligand injection cycle. We believe Peltucetine may provide a better treatment option for patients as it was designed to address the limitations of today's standard of care.

Speaker Change: Thank you.

Joseph Schwartz: Our next question is from Joseph Schwartz of LeeRink Partners. Great. Thanks very much. Invest wishes to mark, of course. That's been great to work with you.

Operator: Our next question is from Joseph Schwartz of Lerink Partners.

Speaker Change: Our next question is from Joseph Schwartz of Leerink partners.

Joseph Schwartz: Great. Thanks very much. And best wishes to Marc, of course. It's been great to work with you. Are specific clinical outcomes being systematically measured in Toucan, or was the observation of two patients who resumed menstruation something that was just noticed? I'm just wondering if there are other clinical benefits that might arise when you report top-line data in the second half. Alan, Dr. Excellents, E.S.

Joseph Schwartz: Great. Thanks, very much and best wishes to Mark of course, that's been great to work with you.

Joseph Schwartz: Are specific clinical outcomes being systematically measured in 2KAN, or was the observation of two patients who resumed menstruation something that was just noticed?

Speaker Change: Our specific clinical outcomes being systematically measured in two can or was the observation of two patients who resumed menstruation something that was just.

Speaker Change: Noticed.

Alan Krasner: I'm just wondering if there are other clinical benefits that might arise when you report top-line data in the second half?

Speaker Change: Wondering if.

Jim Hazard: Our commercial team has recently launched acromeglytruth.com, our disease awareness campaign for endocrinologist treating patients with acromegly, which you can see on slide 7. More than 1500 providers have already interacted with this site so far. Acromeglytruth.com includes perspectives from patients on injectable SRLs, including injection site reactions, and GI side effects, breakthrough symptoms, and emotional impact of treatment. In addition, we believe that positive data from the acromegly symptom diary, which was one of the secondary endpoints used in the Pathfinder Phase 3 program, will help healthcare practitioners understand the clinical benefits of Peltucetine, which go well beyond biochemical control.

Speaker Change: There are other clinical benefits that arise when you report topline data in the second half.

Alan Krasner: Allen, would you like to say an answer to Joe? Yeah. So, in addition to our standard endocrine biomarkers to assess disease state in CH. There's a large number of clinical parameters that are observed as part of any clinical trial. But in particular, this one, we do follow certain things very carefully, particularly menstrual functions. We have menstrual diaries in these trials, for example. We also look at metabolic control in other ways using various kinds of blood testing. We know that, for example, glucose is an important parameter in these patients and other like measures. There's actually going to be a large number of what I would call patient-reported outcomes and also position-reported outcomes.

Alan Krasner: Alan, would you like to answer, Joe? Yeah, so in addition to our standard endocrine biomarkers to assess disease state in CAH, there's a large number of clinical parameters that are observed as part of any clinical trial. But in particular, this one, we do follow certain things very carefully, particularly menstrual function. We have menstrual diaries in these trials, for example. We also look at metabolic control in other ways, using various kinds of blood testing.

Alan Jackson: Alan Jackson answer Joe.

Speaker Change: So in addition to our standard endocrine Biomarkers.

Alan Jackson: Assess disease state.

Alan Jackson: CAH.

Alan Jackson: Large number of.

Alan Jackson: Clinical parameters that are observed.

Alan Jackson: And part of as part of any clinical trial, but in particular this one.

Alan Jackson: We do follow certain thanks, very carefully, particularly menstrual function, we have menstrual diaries and needs in these trials. For example, we also look at.

Alan Jackson: Metabolic control and other ways using.

Alan Jackson: Areas.

Alan Jackson: Blood testing and we know that.

Alan Krasner: We know that, for example, glucose is an important parameter in these patients and other like measures. There's actually going to be a large number of what I would call patient-reported outcomes and also physician-reported outcomes, both in phase two, but even more importantly in phase three, when we have larger numbers of patients to assess of both sexes. Very helpful. Thanks, Alan. We'll take our next question from Gavin Clark Gartner of Evercore ISI.

Alan Jackson: For example, glucose as an important parameter in these patients and other.

Jim Hazard: In fact, we have already shared some of this data from the acromegly symptom diary at Endo this past June. We hope this data will help physicians understand the potential transformative impact of Peltucetine for their patients. We already have strong relationships with academic key opinion leaders in the pituitary treatment centers. As another example of our commercial execution, we are looking to expand our relationship with endocrinologists in the community setting. To that end, we've assembled an initial team of thought leader liaisons who are in the field, deepening our relationships with clinical endocrinologists who are managing patients day in and day out.

Alan Jackson: Like measures.

Speaker Change: There is actually going to be a large number what I would call patient reported outcomes and also physician reported outcome.

Alan Krasner: Both in phase 2, but even more importantly in phase 3 when we have larger numbers of patients to assess, of both genders - very helpful.

Alan Jackson: Yes.

Alan Jackson: Both in phase two but even more importantly in phase III, when we have larger numbers of patients to assess both genders.

Alan: Very helpful. Thanks, Alan.

Alan Krasner: Thank you.

Alan Jackson: Okay.

Gavin Clark: We'll take our next question from Gavin Clark-Gartner of Evercore ISI. Your line is open. Hey guys, thanks for taking the question.

Operator: We'll take our next question from Gavin Clark Gartner of Evercore ISI. Your line is open.

Speaker Change: We will take our next question from Gavin Clark Gartner of Evercore ISI. Your line is open.

Speaker Change: Hey, guys. Thanks for taking the question I just wanted to ask more specifically on the carcinoid regulatory feedback as we're getting close to that what's your desired base case or expectation on primary endpoint.

Gavin Clark: I just wanted to ask more specifically on the Carsonoid regulatory feedback as we're getting close to that. What's your desired base case or expectation on primary endpoint? Confident that a placebo comparator arm will be viable.

Jim Hazard: The second pillar of our commercial plan is empowering patients to ask for better care and improve control of their symptoms. We recognize the vital role patients play in advocating for their diagnosis, managing their disease and seeking optimal treatment. To this end, we plan to launch next year an expanded disease awareness campaign targeted towards patients with acromegly. The goal is to help patients realize that better control of their acromegly symptoms and the lower treatment burden may be possible.

Speaker Change: <unk> that a placebo comparator arm will be viable and also just reconfirm youre looking at both switch and new starts and confirming the dose would be within the same one trial. Thank you.

Gavin Clark: And also just reconfirm you're looking at both switch and new starts and confirming those would be within the same one trial.

Gavin Clark: Thank you. Okay, thanks.

Unknown Executive: Okay, thanks. As far as the patient population, we're definitely intending to include both previously treated and naive patients. I think that, you know, we have looked at a lot of different ways to estimate efficacy. And since there's no real sort of guidance from FDA in this indication, it's a little bit, you know, sort of ours to propose, right? So, I think that, you know, we'd rather kind of have the discussions first and then disclose where we're going, you know, after we've designed the trial.

Speaker Change: Okay. Thanks.

Alan Krasner: As far as the patient population, we're definitely intending to include both previously treated and naive patients. I think that we have looked at a lot of different ways to estimate efficacy. And since there's no real sort of guidances from FDA in this indication, it's a little bit sort of ours to propose.

Speaker Change: As far as the.

Speaker Change: The patient population we're definitely.

Speaker Change: And pending to include both.

Alan Jackson: Previously treated and nave patients.

Speaker Change: I think that.

Alan Jackson: We have.

Speaker Change: Looked at a lot of different ways to estimate efficacy.

Jim Hazard: Ultimately, we want to empower patients to ask their health care practitioner for Peltucetine once approved. As Dana mentioned, our patient advocacy team has been engaging with the acromegly patient organizations since early in clinical development. We are continuing to strengthen our relationship with the patient community to ensure we are addressing the needs of patients. The third pillar of our commercial plan is to ensure optimal patient access to our best-in-class therapy. The national account team responsible for all payer interactions is in place and onboarded.

Speaker Change: And since there is no real sort of.

Speaker Change: Guidance is from FDA in this indication.

Speaker Change: It's a little bit sort of.

Speaker Change: Ours to propose right so.

Alan Krasner: So I think that we'd rather kind of have the discussions first and then disclose where we're going after we've designed the trial. Thanks, Evan, that you asked. It's just reconfirm whether placebo or an active comparator arm may be required. Our plan is that a placebo trial will be required. Yep.

Speaker Change: I think that.

Alan Jackson: We'd rather kind of have the discussions first and then.

Speaker Change: Disclose where we're going.

Speaker Change: After we've designed the trial.

Unknown Executive: Is there anything else, Gavin, that you asked? It's just reconfirming whether placebo or an active comparator arm may be required. Our plan is that at placebo, a trial will be required. Our next question is from Brian Skorney of Baird.

Kevin: Thanks, Kevin.

Speaker Change: Hey, you asked.

Alan Jackson: Okay.

Speaker Change: I was just reconfirming, whether placebo or an active comparator arm maybe required.

Jim Hazard: We have had discussions with the top commercial and government payers covering the majority of lives in the country and initial feedback from those payer advisory meetings has been encouraging. Patient Support Center to help streamline the prescribing dispensing and reimbursement process. This support center is being designed based on our ongoing market research and discussions with patients to develop best practices and close the gaps in the current reimbursement processes. We have also finalized our distribution channel.

Speaker Change: Our plan is that a placebo trial will be required.

Ryan Scorney: Thanks.

Kevin: Great. Thanks.

Alan Jackson: Okay.

Ryan Scorney: Our next question is from Ryan Scorney of Baird.

Brian <unk>: Our next question is from Brian <unk> of Baird.

Charlie Moore: Hi, this is Charlie on for Brian. Thanks for taking our question.

Unknown Executive: I, uh...

Alan Jackson: Hi, This is Charlie on for Brian. Thanks for taking our question. So just thinking about the profile of <unk>. We've seen so far do you have any plans to investigate it and the treatment of neuroendocrine tumors in the future.

Alan Krasner: So just thinking about the profile of Peltusatine we've seen so far, do you have any plans to investigate it in the treatment of neuroendocrine tumors in the future? So we are creating it to treat neuroendocrine tumors in those patients that experience the symptoms of carcinoid syndrome. So perhaps you're referring to understanding the anti-tumor activity that's well described as part of a smash that receptor ligands on these tumor types.

Alan Jackson: Hello.

Unknown Executive: We are using it to treat neuroendocrine tumors in those patients that experience the symptoms of carcinoid syndrome. So, perhaps you're referring to understanding the anti-tumor activity that's well described as part of somatostatin receptor ligands on these tumor types. And so we are thinking that as part of our phase three, we will be observing tumors, both in the phase three study in itself and an open-label extension. But we're not designing the trial to measure anti-tumor activities, as we think we've got a wide range of other areas we should be investing in.

Speaker Change: We are using it to treat neuroendocrine tumors and those patients that experienced the symptoms of carcinoid syndrome.

Jim Hazard: We look forward to sharing more details at our next earnings call. In addition to establishing the commercial foundation for a successful launch, our medical affairs team is engaging in robust scientific discussions throughout the medical community. We've hired Dr. Bob Cuddy, an experienced endocrinologist who has dedicated much of his career to treating patients, including those with acromegally, and has built and led medical affairs functions at other organizations such as Jensen, Santa Fe, and Amgen.

Speaker Change: So, perhaps you're referring to.

Speaker Change: Understanding the anti tumor activity, that's well described as part of <unk>.

Speaker Change: <unk> receptor ligands on these tumor types and so we are thinking that as part of our phase III, we will be.

Alan Krasner: And so we are thinking that, as part of our phase three, we will be observing tumors both in the phase three study in itself and in open label extensions, but we're not designing the trial to measure anti-tumor activities. As we think we've got a wide range of other areas we should be investing in and that the treatment of patients with neuroendocrine tumors is moving more and more to somatostatin analogs for symptom control, and other modalities are coming in play for treatment of the tumor growth itself.

Speaker Change: Observing.

Speaker Change: Tumors.

Speaker Change: In the phase III study in itself in an open label extensions.

Speaker Change: But we're not designing the trial to measure anti tumor activities as we think we've got.

Jim Hazard: In conclusion, chronetics continues our evolution to ensure that we are in the best position to execute our launch strategy following approval. The Paltucetine data that have been generated to date puts us in a unique position to demonstrate a highly differentiated clinical profile across multiple dimensions, including biochemical control, symptom control, tolerability, and the overall patient experience. We know what is important to patients, to the physicians who treat them, and to the health care system.

Speaker Change: A wide range of other areas, we should be investing in and that the treatment of patients with neuroendocrine tumors.

Unknown Executive: And that the treatment of patients with neuroendocrine tumors is moving more and more to somatostatin analogs for symptom control, and other modalities are coming into play for treatment of the tumor growth itself. And I think you'll hear more from us in the coming quarters about some of these details.

Speaker Change: Moving more and more to somatostatin analogs for symptom control and other modalities are coming in play for treatment of the tumor growth itself.

Alan Krasner: And I think you'll hear more from us in the coming quarters about some of these details. Thank you.

Speaker Change: And I think you'll hear more from us in the coming quarters about some of these details.

Speaker Change: Yeah.

Speaker Change: Thank you.

Speaker Change: Okay.

Catherine Novack: We'll take our next question from Catherine Novack of Jones Research.

Operator: We'll take our next question from Catherine Novack of Jones Research.

Speaker Change: We will take our next question from Catherine Novack of Jones Research.

Jim Hazard: And we believe in the value proposition of Paltucetine, which serves each of these constituencies well. Over the coming months leading up to the expected launch in 2025, we will continue to implement our commercial strategy and share updates along the way. I believe in the transformative potential of Paltucetine for patients with acromegally, and I'm excited to be leading our commercial team to launch this therapy. We are laying the foundation for a fully integrated pharmaceutical company that will be prepared for future Paltucetine indications, as well as other products in the chronetics pipeline.

Catherine Novack: Hey, good afternoon, guys. If I can just want about the pipeline again, I'm about, here's about the role of SSD3 agonism in ADPKD.

Catherine Novack: Hey, good afternoon, guys. If I can just ask you one about the pipeline again, I'm very curious about the role of SSC3 agonism in ADPKD. You can just talk about, you know, your decision to go into ADPKD and how this approach might differ from earlier studies that looked at anti-proliferative drugs, which seem to reduce kidney volume but not necessarily improve kidney pulse.

Catherine Novack: Hey, good afternoon guys.

Speaker Change: If I can just one about the pipeline again about.

Speaker Change: I'm curious about the role of FSC three agonism in ADP, Kathy and Ivan just.

Scott Strothers: You can just talk about, you know, your decision to go into ADPKD and how this approach might differentiate from earlier studies that looked at and had prolificative drugs, which seemed to reduce kidney volume, but not necessarily improve kidney function for, say. Yeah, no, thanks, Catherine, and that question could justify a half-a-day conversation about the science here. But it's fairly remarkable that as we were looking through the literature just in our day-to-day scientific reading, we noticed that the people studying psiliopathy, of which polycystic kidney is one of the manifestations of the psiliopathy. That everybody was using an antibody against SSD3 as a cytologic marker for immunostaining of the psiliopathy.

Speaker Change: Talk about.

Speaker Change: Your decision to go into ADP JV and how this approach might differentiate from earlier studies that looked at.

Speaker Change: Anti proliferative drugs, which seem to reduce kidney volume, but not necessarily improved kidney.

Unknown Executive: Kidney Function Per Se.

Speaker Change: Function.

Unknown Executive: Yeah, no, thanks, Catherine. And that question could justify a half-day conversation about the science here. But it's fairly remarkable that as we were looking through the literature just in our day-to-day scientific reading, we noticed that the people studying ciliopathies, of which polycystic kidney is one of the manifestations of the ciliopathies, everybody was using an antibody against SST3 as a cytologic marker for immunostaining of the cilia. So SST3 is expressed very... cleanly in Philadelphia.

Speaker Change: Yeah, no. Thanks, Katherine and that that question could justify a half a day conversation about the science here.

Marc Wilson: With that, I will now hand it over to Mark to review the financials. Thank you, Jim.

Speaker Change: But it is fairly remarkable that as we were looking through the literature just in our day to day scientific reading.

Marc Wilson: As Scott mentioned, I will be stepping down from my role as CFO at Chronetics for personal reasons. Chronetics is in very capable hands with its deep bench of leaders across the organization. I am proud of all the way of accomplished during my tenure, and I look forward to the company's continued success, and it evolves into a fully integrated endocrinology franchise.

Speaker Change: We noticed that people studying ciliopathy of which polycystic kidney assay.

Speaker Change: One of the manifestations of the Ciliopathy east that.

Speaker Change: That everybody was using an antibody against <unk> three as a cytologic marker for immuno staining of the of the cilia.

Scott Strothers: So, SSD3 has expressed very cleanly in psiliopathy, and we know that the psiliopathy is that are caused by mutations in polycystins, which resulted in an imbalance of the cyclic AMP and calcium ratio in the psiliop, and also metastatic with too much cyclic AMP. And also metastatic analogs are acting; also metastatic receptors are acting to decrease cyclic AMP levels in cells, and in this case in the primary psiliopathy. So, we'll be coming out with more and more data around this, but we've developed animal models in genetically engineered mice. We've done cyst models and dispersed kidney cells.

Marc Wilson: With that, I will now return review the second quarter financial results. Prinetics continues to be in a strong financial position having ended the second quarter with approximately $863 million in cash and investments. Our solid financial foundation is projected to fund our current operating plan into 2020. This includes plans to commercialize Peltusatine for Acro-Megley, the initiation of multiple later stage clinical trials in additional indications with Peltusatine and Anti-Mailment, as well as continued investment in our pipeline.

Speaker Change: So <unk> three is expressed very.

Speaker Change: Cleanly and cilia.

Unknown Executive: And we know that the ciliopathies are caused by mutations in polycystins, which results in an imbalance of the cyclic AMP and calcium ratio in the cilia, and all somatostatin analogs are acting, all somatostatin receptors are acting to decrease cyclic AMP levels in cells and, in this case, in the primary cilia. So, we'll be coming out with more and more data around this, but we've developed animal models in genetically engineered mice. We've done cyst models in dispersed kidney cells. We've done signaling.

Speaker Change: And we know that the Ciliopathy ciliopathy, it's that are caused by mutations in poly systems, which.

Speaker Change: Which resulted in an imbalance of the cyclic A&P and calcium ratio in the cilia and all somatostatin with too much cyclic EMP.

Speaker Change: And also Matt a statin analogs.

Speaker Change: <unk> also met a statin receptors are acting to decrease cyclic A&P levels in cells and in this case the primary cilia.

Speaker Change: So we will be coming out with more and more data around this but we have developed.

Speaker Change: Animal models.

Marc Wilson: With respect to the second quarter financial results, research and development expenses were $58.3 million for the quarter end of June 30, 2024 compared to $40.6 million for the same period in 2023. The increase was primarily attributable to higher personnel costs and manufacturing and development activities, both of which were driven by the advancement of our clinical programs and the expansion of our pre-clinical portfolio. For the quarter end of June 30, 2024, general and administrative expenses were $24.8 million compared to $13.3 million for the same period in 2023.

Speaker Change: <unk> genetically engineered mice, we've done.

Speaker Change: This models and disperse kidney cells.

Scott Strothers: We've done signaling. We've done a variety of things to begin to shore up the hypothesis that activating the SSD3 will be effective in polycystic kidney disease, but of course the real test is to get it into patients and see what it does. So, that's what we're trying to figure out how to get there, whether either ourselves or through partners. But a huge unmet need, and just as a hint, you know, we don't expect, based on the location in the renal tubules, that this will cause the type of very high urine volumes that you see with the phase of press and antagonists like 12 aptam.

Speaker Change: We've done signaling we've done a variety of things to begin to shore up the hypothesis that activating the <unk> will be effective in polycystic kidney disease, but of course, the real test is to get it into patients and see what it does.

Unknown Executive: We've done a variety of things to begin to shore up the hypothesis that activating SST3 will be effective in polycystic kidney disease. But, of course, the real test is to get it into patients and see what it does. So that's what we're trying to figure out how to get there, whether either ourselves or through partners, but a huge unmet need. And just as a hint, you know, we don't expect based on the location in the renal tubules that this will cause the type of very high urine volumes that you see with the vasopressin antagonists like tulbap. And that's one of the major limiting tolerability issues around the use of tell-opt-ins.

Speaker Change: So that's what we're trying to figure out how to get there whether either ourselves or through partners, but a huge unmet need and just as a hint. We don't expect based on the location and the renal tubule statistical caused the type of.

Marc Wilson: The change was primarily due to an increase in personnel costs and an increase in outside services as we continue to build the infrastructure to support our growing pipeline. Net loss for the quarter end of June 30, 2024 was $74.1 million compared to a net loss of $51 million for the same period in 2023. The revenues were $0.4 million for the quarter end of June 30 compared to $1 million for the same period in 2023.

Speaker Change: Very high year end volumes that you see with the with the phase of Crescent antagonist like <unk>.

Scott Strothers: And that's one of the major limiting tolerability issues around the use of top aptam. Right. Well, thanks.

Speaker Change: And that's one of the major limiting tolerability issues around the use of <unk>.

Speaker Change: Alright.

Unknown Executive: Well, thanks. I'm definitely looking forward to hearing more from that program in the future. Super exciting. Very high on my needs list. We'll take our next question from John Wolleben of Citizens JMP.

Scott: Well thanks Scott.

Scott Strothers: Definitely looking forward to hearing more from that program in the future. Super exciting. Very high on met need.

Speaker Change: Looking forward to hearing more from that program in the future.

Speaker Change: Super exciting.

Speaker Change: High unmet need.

John Wallabin: We'll take our next question from John Wallabin of Citizens JMP.

Speaker Change: We will take our next question from John Walden of citizens JMP.

Marc Wilson: Revenues during the current year's quarter were derived from the Peltusatine licensing arrangement with our Japanese partner SKK. Net cash used for operating activities for the quarter end of June 30, 2024 was $45.6 million. We expect our cash burn to be approximately $50 to $60 million per quarter for the remainder of 2024.

John Wallabin: Hey, good afternoon. Thanks for taking the question and that's wishes to mark. Let's hope that you guys could talk a little bit about how you're thinking about next steps, just simply in CAA.

Operator: Hey, uh, good a

John Walden: Hey, good afternoon. Thanks for taking my question and best wishes to Mark.

John Walden: I was hoping you guys could talk a little bit about how you're thinking about next steps, particularly in CAH. If you think you'd have enough information to move forward to a pivotal trial.

John Wallabin: if you think you'd have enough information to move forward to a pivotal trial on how you think about integrating younger patients into the program as well.

Greg: How are you thinking about it Greg.

Greg: Longer patients into the program as well.

Alan Krasner: Well, thanks so much for the question. We have the full complement of patient data; we will definitely be able to talk to the FDA about the design of phase three. So I think the data that you generate from those three cohorts in that trial will certainly be enough to go talk to the agency about our Phase three design.

Unknown Executive: Well, thanks so much for the question. Yeah, those are definitely, you know, key areas for us in the future. As Alan mentioned and Scott mentioned before, we're really encouraged by the data so far for CAH, and we think that once we have the full complement of patient data, we'll definitely be able to talk to the FDA about the design of Phase 3. So I think the data that we generate from those three cohorts in that trial will certainly be enough to go talk to the agency about our Phase 3 design.

Scott Strothers: I will now hand it back to Scott for closing remarks before we begin Q&A. Thank you, Mark. Looking to the rest of 2024 and 25, we'll continue to build on the strong progress today. We look forward to upcoming clinical and regulatory milestones from Peltusatine and Atumelnet and continued advancement of our deep pipeline of emerging candidates. Chronoetics continues to be well positioned to become the premier, fully integrated, endocrine-focused pharmaceutical company.

Greg: Well thanks, so much for the question.

Greg: Yes, those are definitely key areas for us in the future.

Greg: As Alan mentioned and Scott mentioned before that we're really encouraged.

Speaker Change: The data so far for CAH.

Speaker Change: And we think that once we have the full complement of patient data, we will definitely be able to talk to the FDA about the design of phase III. So I think the data that.

Speaker Change: We generate from those three cohorts in that trial, which certainly be enough to go talk to the agency about our phase III design.

Scott Strothers: Thank you all for your attention.

Unknown Executive: Operator, we're ready to take questions. For folks on the call, we'd appreciate it if you could limit yourself to one question. We have a lot of analysts on the call. I want to ensure that we can provide each of you with a thoughtful response. Thank you very much.

Alan Krasner: And as far as the pediatric program, you know, we're also actively, you know, putting together for a protocol designs to evaluate that in phase two and then be able to use that, you know, to very quickly move into phase three. Because that obviously is a significant on medical need with the profound morbidity, you know, for those kids. So we're very, very focused on that.

Unknown Executive: And as far as the pediatric program is concerned, we're also actively putting together protocol designs to evaluate that in phase two and then be able to use that, you know, to very quickly move into phase three, because that obviously is a significant unmet medical need with profound morbidity for those kids. So we're very, very focused on that. That's helpful; thank you very much. We'll take our next question from Leland Gershell of Oppenheimer. Hey, good afternoon. Thanks for taking my questions. And Marc, it's been great working with you.

Speaker Change: And as far as the pediatric program.

Speaker Change: We're also actively.

Speaker Change: Putting together.

Speaker Change: Protocol designs to evaluate that in phase III, and then be able to use that.

Unknown Executive: And at this time, if you would like to ask a question, please press star one now on your telephone keypad to withdraw yourself from the queue you may press star two.

Speaker Change: Two very quickly move into phase III.

Speaker Change: Because that obviously is a significant unmet medical need with.

Jessica Fye: We'll take our first question from Jessica Fy of JP Morgan. Hey guys, good afternoon. Thanks for taking my question and Mark. It's been great working with you over the years.

Speaker Change: Profound morbidity for those kits so we're very.

Alan Krasner: I was wondering how we should think about what additional insights We could expect to gain from the phase two updates in CAH and Cushing's coming later this year, and what venue or venues we should look for those at. Thank you, Jess.

Speaker Change: Very focused on that.

Unknown Executive: That's awful.

Speaker Change: Okay. That's helpful. Thank you very much.

Leland Gershell: I'll take our next question from Leland Gershell of Oppenheimer. Hey, good afternoon. Thanks for taking my questions, and Mark has been great working with you, and best of luck in the future.

Operator: We'll take our next question from Leland Gershell of Oppenheimer this afternoon.

Leland <unk>: We'll take our next question from Leland <unk> of Oppenheimer.

Leland <unk>: Hey, good afternoon. Thanks for taking my questions and Mark has been great working with you and best of luck.

Alan Krasner: Let me hand that over to Alan to give you a brief. Yeah, you know, we will have finals or top line results in CAH and Cushing's disease hopefully and we will be able to sort of continue to support the messages, I believe, that we have already communicated as the endocrine society, meaning that this appears to be a uniquely effective by agents in these disease states that in terms of biomarker responses, I think, you know, with higher sample sizes will have a greater variety, a greater number of patients evaluated and will have most importantly, probably from the regulatory standpoint, the dose response really to the relationship fully described and I think that's what will trigger that's the information you need to really fully design our case three program and go forward in development.

Speaker Change: In the future.

Scott Strothers: Scott, why don't you ask on your thyro tropin receptor program you'd mentioned recent calls that you've been moving nicely along with potential candidates. Just wondering where you may be there.

Scott: Scott wanted to ask on your thyrotropin receptor.

Scott: Program you'd mentioned recent calls that you've been moving.

Speaker Change: Nicely along with potential candidates.

Scott: Just wondering where you may be there could we see a.

Scott Strothers: Could we see a clinical candidate nominated in the next few months or perhaps in .25. Thanks. Yeah, thanks, Leland.

Speaker Change: Clinical candidate nominated.

Speaker Change: And the next few months or perhaps in 'twenty 'twenty five.

Unknown Executive: Yeah, thanks, Leland. It's always hard to say when you're going to get there. The process of drug discovery is very much an asymptote, and you just keep getting closer and closer and closer to what you think is an ideal candidate. At a certain point, you say, that's good; that's good enough. And I got to say that in a TSH antagonist, where 1 to 2% of the population can have this disease, and we just saw, I just saw the news this morning that one of my favorite characters, Rey, in Star Wars, was just diagnosed with Graves' disease.

Speaker Change: Yes, Thanks, Liana, it's always hard to say when youre going to get there the process of drug discovery is very much an asymptote and you just keep getting closer and closer and closer to what you think is an ideal candidate in a certain point you say that's good that's good enough.

Scott Strothers: It's always hard to say when you're going to get there. The process of drug discovery is very much an asymptote, and you just keep getting closer and closer and closer to what you think is an ideal candidate. And at a certain point you say, that's good, that's good enough. And I got to say that in the TSH antagonist, where one to 2% of the population can have this disease.

Speaker Change: And I got to say that in and of TSH antagonist, where 1% to 2% of the population can have this disease and we just saw.

Scott Strothers: And we just saw, I just saw the news this morning that one of my favorite characters, Ray, and Star Wars was just diagnosed with grave disease. But this molecule needs to be really high quality. So we are working hard on that. I can tell we're really close. But whether that's this quarter, next quarter, early next year, I don't know for sure, but it's right around the corner. Great.

Speaker Change: I just saw the news this morning that.

Speaker Change: One of my favorite characters Ray and Star Wars was just.

Speaker Change: Diagnosed with graves disease.

Unknown Executive: But this molecule needs to be really high quality, so we are working hard on that. I can tell we're really close. But whether that's this quarter, next quarter, or early next year, I don't know for sure, but it's right around the corner.

Alan Krasner: Yeah, and maybe as a quick reminder to those not as close to it as us that we now have the 40 80 and 120 milligram cohorts enrolled and the data from those groups will be available later this year.

Speaker Change: But this molecule needs to be really high quality. So we are working hard on that I can I can tell we're really close.

Speaker Change: But whether that's this quarter next quarter early next year I don't know for sure, but it's it's right around the corner.

Unknown Executive: Thank you.

Yasmeen Rahimi: We'll take our next question from Yasmeen Rahimi of Piper Sandler.

Speaker Change: Great. Thank you.

Douglas Tsao: We'll take our next question from Douglas Sal of HC Wainwright. Hi, good afternoon. Thanks for taking the questions.

Operator: We'll take our next question from Douglas Tsao of H.C. Wainwright.

Speaker Change: We will take our next question from Douglas Tsao of H C. Wainwright.

Yasmeen Rahimi: Mark, we're going to greatly miss you. It's been really a pleasure working with you and we have done a tremendous job. So we will definitely miss you and hope the search continues for a little longer so we can continue working with you.

Speaker Change: Sure.

Douglas Tsao: Hi, good afternoon. Thanks for taking the questions. And I'll join the chorus of people saying how much we've enjoyed working with Marc over the years.

Douglas Tsao: Hi, good afternoon, thanks for taking the questions and ill join the chorus of people, saying, how much reis enjoyed working with mark over the years.

Douglas Tsao: And I'll join the course of people saying how much we've enjoyed working with Mark over the years. I guess.

Dana Pizzuti: I wanted to ask just a question on carcinoid. If you could provide some color around engagement with the agency, where are you in terms of the sign off? And what sort of left to do to kick off the registration study and I'll jump back into the queue. Yeah. Thanks, Danny. You want to handle that one? Well, yeah, we've just completed all the analyses that we needed to do and are essentially ready to start the process of engaging with them so it shouldn't take too long to get that squared away.

Speaker Change: I guess.

Jim Hazard: You know, maybe a question for Jim, since he mentioned, you know, the fact that patients often have a very different experience of acramegly than clinicians realize. So I guess in terms of driving adoption, you know, how do you plan to get around that? Because I think that has been a factor that has, you know, hampered, there was the launch of my caps, you know, in terms of converting that product.

James Hassard: You know, maybe a question for Jim, since he mentioned the fact that patients often have a very different experience with acromegaly than clinicians realize. So I guess in terms of driving adoption, you know, how do you plan to get around that? Because I think that has been a factor that has, you know, hampered the launch of myCapsa, you know, in terms of converting that product. And I know that Paltustin's profile is very different; you have much, much stronger data. But, you know, just how do you, from a tactical standpoint, plan to address that aspect of the launch? Thank you.

Jim Hazard: A question for Jim.

Speaker Change: Since you mentioned, the fact that patients often have a very different experience with acromegaly.

Douglas Tsao: Then clinicians realize so I guess in terms of driving adoption.

Speaker Change: How do you plan to get around that because I think that has been a factor that has hampered there was the launch of my caps.

Speaker Change: In terms of converting that product and I know that the participants profile is very different.

Jim Hazard: And I know that the, you know, how two students four files, very different on much much stronger data, but you know, just how do you promote from a tactical standpoint plan to address that aspect of the launch. Thank you.

Speaker Change: Much much stronger data, but just.

Douglas Tsao: Just how do you from a from a.

Speaker Change: Tactical standpoint plan to address that aspect of the launch thank you.

Dana Pizzuti: As we mentioned, we're expecting to get the trial up and running by the end of the year. So, you know, we have not, you know, yet completed the discussions with them. So, you know, we're sort of actively involved.

Speaker Change: Sure.

Jim Hazard: Thanks, Doug, and I think, you know, we'll all start where you've left off, which is, yeah, we've got a great product in Peltusatine. And that's something that does differentiate us, certainly, from most recent launches.

James Hassard: Thanks, Doug. And I think, you know, I'll start where you left off, which is, yeah, we've got a great product in Peltucetine. And that's something that differentiates us, certainly from most recent launches. But, however, it is true that even with such a great product, what we hear from physicians is, "If it's not broken, I'm not going to fix it." And that's exactly the purpose and the rationale behind our disease state campaign, acromegalytruth.com.

Douglas Tsao: Thanks, Doug and I think.

Speaker Change: Well I'll start.

Douglas Tsao: You left off which is yes, we've got a great product in <unk> and Thats something that does differentiate us certainly from <unk>.

Speaker Change: Most recent launches, but however, it is true that even with such a great product. What we hear from physicians is if it's not broken I'm not going to fix it and thats exactly the purpose and the rationale behind.

Jim Hazard: But, however, it is true that even with such a great product, what we hear from physicians is, "if it's not broken, I'm not going to fix it." And that's exactly the purpose and the rationale behind our disease state campaign Acramegly Truth.com. So already, you know, there's a small contingent of endocrinologists that are behind a lot of the data in this area of, again, trying to address this, this discord in dialogue. And it is really making sure that physicians are aware of the patient experience and then ensuring that, you know, as we get closer to launch, that we really do empower patients to have that discussion with their endocrinologist based on the research that we've done.

Jeff Hung: We'll take our next question from Jeff Hound of Morgan Stanley.

Scott Strothers: Thanks for taking my question and best wishes to mark. You mentioned that you may advance your ADPKD program with a partner independently. What would be the deciding factors for Connection to go with one strategy versus the other? Is that only relevant to this program or are there specific early stage programs that you would not be opening open to partnering?

Douglas Tsao: Our disease State campaign, Acromegaly truths dot com so.

James Hassard: So already, you know, there's a small contingent of endocrinologists that are behind a lot of the data in this area of trying to address this discord in dialogue. And it is really making sure that physicians are aware of the patient experience and then ensuring that, as we get closer to launch, we really do empower patients to have that discussion with their endocrinologist. Based on the research that we've done, Doug, it's a powerful message.

Douglas Tsao: Already.

Douglas Tsao: A small contingent of endocrinologists that are behind a lot of the data in this area of again trying to address this this discord in dialogue and it is really making sure that physicians are aware of the patient experience and then ensuring that as we get closer to launch that we really do in <unk>.

Scott Strothers: Thanks. Well, so there's a couple considerations. Thanks for the question, Jeff. A couple considerations. One is. You know, we've built a remarkably strong team in the under-cannology area and we would need to start building out our kidney capabilities, our nephrology capabilities in order to do justice for this program. That being said, I think that's quite a reasonable thing for us to do as a reminder of the polycystic kidney program and the PTH antagonist program both address nephrology populations.

Scott Strothers: So there would be some synergy there. On the other hand, there may be groups out there that are further advanced in us in the field and could do better justice to this program more rapidly. And I'll also just say that, you know, given the productivity of our discovery group and the depth of our pipeline, I want to make sure that from an internal perspective, we can grow adequately to give each program its due resources and attention. And so that growth of the company is a factor as well and a very fortunate position to be able to have to make choices like this.

Unknown Executive: Right, thank you.

Douglas Tsao: Our patients to have that discussion with their endocrinologist.

James Hassard: And I know that physicians have reacted well to the awareness. And I will tell you that patients even react better to it when they see the campaign and realize that, yes, this is the kind of discussion, these are the kinds of symptoms that they're feeling. This is what they want. This is the kind of discussion they want to have with their endocrinologist. So more to come, and we'll be providing details as to how impactful this is and what the metrics are from the campaign, but it is really that. The underpinning of a great product is awareness around the problem.

Douglas Tsao: Based on the research that we've done Doug, it's a powerful message and I know that the physicians have reacted well to the awareness and I will tell you that patients even react better to it when they see the campaign.

Jim Hazard: Doug, it's a powerful message, and I know that the physicians have reacted well to the awareness. And I will tell you that patients even react better to it when they see the campaign and realize that yes, this is the kind of discussion. These are the kinds of symptoms that they're feeling. This is what they want. This is the kind of discussion they want to have with their endocrinologist. So more to come, and we'll be providing, you know, details as to, you know, how impactful this is and what the metrics are from the campaign.

Doug: And realize that yes. This is the kind of discussion. These are the kinds of symptoms that they are feeling.

Speaker Change: This is what.

Speaker Change: They want this is the kind of discussion they want to have with their endocrinologists. So more to come in and we will be providing details as to how impactful. This is and what the metrics are from the campaign.

Jim Hazard: But it is really that the underpinning of a great product is the awareness around the problem. Okay, great. Thank you so much. And that's helpful. Thanks, Doug.

Speaker Change: But it is it is really that.

Speaker Change: The underpinning of our great product is the awareness around the problem.

Unknown Executive: Okay, great. Thank you so much. That's very helpful.

Speaker Change: Okay, great. Thank you so much and thats helpful.

Doug: Thanks, Doug.

Operator: And we'll take a question from Cory Jubinville of Lifesci Capital.

Corey Jubinville: And we'll take a question from Corey Juvenville of Lifestyle Capital. Hey, thanks for taking our questions, and congrats on all the progress. And Mark, congrats on everything you've helped build over the years. We'll definitely be sad to see you go, but of course, wish you well and whatever comes next. But I guess can you help give us a bit of context in how your lawn shepherds in acromegly could potentially help support a launch in carcinoid syndrome down the line thinking about these prescriber groups is almost like a Venn diagram. How might a carcinoid patient, how often might a carcinoid patient be coming in contact with an endocrinologist that might have had previous experience with peltus teen treating acromegallics and, you know, while it's certainly been several errors ago.

Speaker Change: And we'll take a question from Corey Dubin Vale of Lifesize capital.

Cory Jubinville: Hey, thanks for taking our questions and congrats on all the progress. And Marc, congrats on everything you've helped build over the years. We'll definitely be sad to see you go, but, of course, we wish you well in whatever comes next.

Speaker Change: Hey, Thanks for taking our questions and congrats on all the progress and Mark Congrats on everything you've helped build over the years, we will definitely be sad to see you go but of course wish you all and whatever comes next.

Dennis Dean: We'll take our next question from Dennis Dean of Jeffries. Hi, thanks for taking our questions. Maybe if I can ask one on Akram Negoli, curious how you're thinking about the pricing strategy. Once you guys eventually get approved next year, if you plan a price at a premium, give in your north. Thank you so much. Thanks, Dennis. I'll add Jim Handle Allen. Thanks, Dennis.

James Hassard: But I guess, can you help give us a bit of context in how your launch efforts in acromegaly could potentially help support a launch in carcinoid syndrome down the line? Thinking about these prescriber groups as almost like a Venn diagram, how might a carcinoid patient, how often might a carcinoid patient be coming in contact with an endocrinologist that might have had previous experience with palatuce You know, while it's certainly been several eras ago, are there any learnings you're taking from the expansion of octreotide or lanreotide into these patient groups from acromegaly to carcinoid syndrome or GEPNets that can be applied to your strategy with palatucetine?

Speaker Change #100: But I guess can you help give us a bit of context, and how youre launch efforts in acromegaly could potentially help support launching carcinoid syndrome down the line thinking about these prescriber group is almost like a venn diagram.

Speaker Change: Carcinoid page, how often might have carcinoid patient b coming in contact with an endocrinologist that might've had previous experience with <unk> treating acromegalic <unk>.

Jim Hazard: You know, still too early to talk about pricing. We are engaged with, as we mentioned, we are engaged with payers and sharing the value proposition. And again, it has been some encouraging conversations to date. But again, we just need to have a deeper look at a number of factors before we disclose pricing, probably next year. Thank you.

Speaker Change: While it's certainly been several areas ago.

Corey Jubinville: Are there any learnings you're taking from the expansion of ox reattied or land reattied into these patient groups from acromegaly to carcinoid syndrome or gap nets that can be applied to your strategy with peltus?

Speaker Change: Are there any learnings you're taking from the expansion of Octreotide or land Ria tied into these patient groups from acromegaly to carcinoid syndrome or <unk>.

Speaker Change: That can be applied to your strategy with <unk>.

Jim Hazard: Pizzuti. Thanks, Corey. We have already started to look at the overlap in terms of the customer base. And I'll tell you where we see a great deal of overlap is in the pituitary treatment centers. So the same academic centers; there are about 45 of these pituitary treatment centers. And there is a good deal of overlap with, for example, the NCCN Cancer Network, the National Comprehensive Cancer Network. So places like Memorial Sloan Kettering, you know, Dr. Eliza Geer is at MSK; that's also obviously a cancer institution. And as well, to your point, there are, you know, specific endocrinologists that are very much involved in neuroendocrine tumors as well.

James Hassard: You know, thanks. Thanks, Cory.

Speaker Change: Thanks, Corey we have already started to look at the overlap in terms of the customer base and I'll tell you where we see.

Joseph Schwartz: Our next question is from Joseph Schwartz of LeeRink Partners. Great. Thanks very much. Invest wishes to mark, of course. That's been great to work with you.

Speaker Change: Great deal of overlap is in the pituitary treatment centers. So the same academic centers. There are about 45 of these pituitary treatment centers and there is.

Alan Krasner: Are specific clinical outcomes being systematically measured in 2KAN, or was the observation of two patients who resumed menstruation, something that was just noticed? I'm just wondering if there are other clinical benefits that might arise when you report top-line data in the second half? Allen, would you like to say an answer to Joe? Yeah. So in addition to our standard endocrine biomarkers to assess disease state in CH. There's a large number of clinical parameters that are observed as part of any clinical trial.

Speaker Change #103: A good deal of overlap with for example, <unk> and.

Speaker Change: CCM cancer network, the National comprehensive cancer network. So places like Memorial Sloan Kettering, Dr. Elisa gear is that M. S. K Thats also obviously, a cancer institution and as well to your point there are.

James Hassard: We have already started to look at the overlap in terms of the customer base, and I'll tell you where we see a great deal of overlap is in the pituitary treatment centers. So at the same academic centers, there are about 45 of these pituitary treatment centers. And there is, you know, a good deal of overlap with, for example, the NCCN cancer network, the National Comprehensive Cancer Network. So places like Memorial Sloan Kettering, you know; Dr. Eliza Gere is at MSK.

James Hassard: That's also obviously a cancer institution. And as well, to your point, there are, you know, specific endocrinologists that are very much involved in neuroendocrine tumors as well. So there is also an overlap. It will be, though, you know, it will be a new indication for us to get into, and oncologists are going to be a new audience for us. But again, where they're located is a lot of co-location and a great opportunity for us. And maybe I'll just go.

Speaker Change: Specific endocrinologists that are very much involved in neuroendocrine tumors as well. So there is also an overlap it will be it.

Jim Hazard: So there is also an overlap. It will be though, you know, there's, it will be a new indication for us to get into and oncologists are going to be a new audience for us, but again, where they're located is a lot of co-location and in a great opportunity for us. And maybe I'll just add to that, Corey, that beyond the actual practicing physicians and their staff, you know, launching your first drug is an exercise in building out a range of different capabilities, relationships with those institutions, the pharmacies of those institutions, relationships with the patients. And, as I mentioned, just our internal capabilities.

Speaker Change: It will be a new indication for us to get into and oncologists are going to be.

Speaker Change: A new audience for us, but again, where they are located.

Speaker Change: Is a lot of co location and a great opportunity for us.

Alan Krasner: But in particular, this one, we do follow certain things very carefully, particularly menstrual functions. We have menstrual diaries in these trials, for example. We also look at metabolic control in other ways using various kinds of blood testing. We know that, for example, glucose is an important parameter in these patients and other like measures. There's actually going to be a large number of what I would call patient-reported outcomes and also position-reported outcomes. Both in phase 2, but even more importantly in phase 3 when we have larger numbers of patients to assess, of both gender- Very helpful.

James Hassard: And maybe I'll just add to that, Cory, beyond the actual practicing physicians and their staff. You know, launching your first drug is an exercise in building out a range of different capabilities, relationships with those institutions, the pharmacies at those institutions, relationships with the payers, and, as I mentioned, just our internal capabilities. So there's a huge amount of synergy between this and then the second launch, and then that, of course, also supports the third launch and fourth launches with Atum LNAT and then the many, many other launches we anticipate with other things coming out of the pipeline.

unknown: [inaudible]

Speaker Change: And maybe I'll, just add to that or is it beyond the actual practicing physicians and their staffs.

Unknown Executive: Thank you.

Speaker Change #105: Launching your first drug as an exercise in building out a range of different capabilities relationships with those institutions. The pharmacies that those institutions relationships with the payers and as I mentioned, just our internal capabilities. So there is a huge amount of synergy.

Scott Strothers: So there's the huge amount of synergy between this and then the second launch. And then that, of course, also support the third launch and fourth launches with AttumelNet. And then the many, many other launches we anticipate with other things coming out of the pipeline.

Speaker Change: <unk>. This and then the second launch and then that of course also support the third launch and fourth launches with <unk> Mellon that and then many many other launches we anticipate there's other things coming out of the pipeline.

Speaker Change: Yeah.

Gavin Clark-Gartner: We'll take our next question from Gavin Clark-Gartner of Evercore ISI. Your line is open. Hey guys, thanks for taking the question. I just wanted to ask more specifically on the Carsonoid regulatory feedback as we're getting close to that. What's your desired base case or expectation on primary endpoint? Confident that a placebo comparator arm will be viable. And also just reconfirm you're looking at both switch and new starts and confirming those would be within the same one trial.

Unknown Executive: Excellent. Thank you for your questions.

Speaker Change #107: Excellent thanks for taking my questions.

Unknown Executive: Thank you.

Speaker Change #103: Thank you.

Unknown Executive: And there are no further questions at this time.

Operator: And there are no further questions at this time. I'd be happy to return the call to our hosts for any closing comments. Thank you all.

Speaker Change #102: And there are no further questions at this time I'd be happy to return the call to our host for any closing comments.

Unknown Executive: I'd be happy to return the call to our hosts for any closing comments. Thank you all for being here and listening to us. And those of you who have such affection for Mark, he's not going anywhere right away, and you know how to find him. And I'm sure you'd be happy to have a drink and launch your ice cream and catch up sometime. Thank you all for listening.

Scott Struthers: Thank you all for being here and listening to us, and those of you who have such affection for Marc, he's not going anywhere right away, and you know how to find him, and I'm sure he'd be happy to have a drink or lunch or ice cream and ketchup sometimes.

Speaker Change #108: Thank you all for being here and listening to us and those of you who have such affection for Mark He is not going anywhere right away and you know how to find them and I'm sure he'd be happy to have a drink.

Speaker Change #105: Our lunch or ice cream and a.

Speaker Change #105: Catch up some time.

Speaker Change #102: Thank you all for listening.

Gavin Clark-Gartner: Thank you. Okay, thanks. As far as the patient population we're definitely intending to include both previously treated and naive patients. I think that we have looked at a lot of different ways to estimate efficacy. And since there's no real sort of guidances from FDA in this indication, it's a little bit sort of ours to propose.

Speaker Change #102: Okay.

This does conclude today's Kinetics Pharmaceuticals, second quarter 2024 earnings conference call. Thank you for participating. You may now disconnect your line and have a great day. Thank you.

Speaker Change #102: Okay.

Operator: This does conclude today's Crinetics Pharmaceuticals second quarter 2024 earnings conference call. Thank you for participating. You may now disconnect your line and have a great day.

Speaker Change #109: This does conclude today's kinetics pharmaceuticals second quarter 2024 earnings conference call.

Speaker Change #102: You for participating you may now disconnect your lines and have a great day.

Speaker Change #102: Uh-huh.

Speaker Change #102: Okay.

Speaker Change #102:

Speaker Change #102: Sure.

Speaker Change #102: [music].

Speaker Change #102: Yes.

Speaker Change #102: Uh huh.

Speaker Change #102: [music].

Gavin Clark-Gartner: So I think that we'd rather kind of have the discussions first and then disclose where we're going after we've designed the trial. Thanks Evan, that you asked. It's just reconfirm whether placebo or an active comparator arm may be required. Our plan is that a placebo trial will be required. Yep. Thanks.

Speaker Change #102: Okay.

Speaker Change #102: [music].

Ryan Scorney: Our next question is from Ryan Scorney of Baird.

unknown: Copyright 2020, New Thinking Allowed Foundation. The End

Speaker Change #102: Uh-huh.

Speaker Change #102: Okay.

Speaker Change #102: Hum.

Scott Strothers: Hi, this is Charlie on for Brian. Thanks for taking our question. So just thinking about the profile of Peltusatine we've seen so far, do you have any plans to investigate it in the treatment of neuroendocrine tumors in the future? So we are creating it to treat neuroendocrine tumors in those patients that experience the symptoms of carcinoy syndrome. So perhaps you're referring to understanding the anti-tumor activity that's well described as part of a smash that receptor ligands on these tumor types.

Scott Strothers: And so we are thinking that as part of our phase three, we will be observing tumors both in the phase three study in itself and in open label extensions, but we're not designing the trial to measure anti tumor activities. As we think we've got a wide range of other areas we should be investing in and that the treatment of patients with neuroendocrine tumors is moving more and more to somatastatin analogs for symptom control and other modalities are coming in play for treatment of the tumor growth itself. And I think you'll hear more from us in the in the coming quarters about some of these details. Thank you.

Catherine Novack: We'll take our next question from Catherine Novack of Jones Research. Hey, good afternoon, guys. If I can just want about the pipeline again, I'm about, here's about the role of SSD3 agonism in ADPKD.

Scott Strothers: You can just talk about, you know, your decision to go into ADPKD and how this approach might differentiate from earlier studies that looked at and had prolificative drugs, which seemed to reduce kidney volume, but not necessarily improve kidney function for say. Yeah, no, thanks, Catherine, and that's, that question could justify a half a day conversation about the science here. But it's fairly remarkable that as we were looking through the literature just in our day-to-day scientific reading, we noticed that the people studying psiliopathy of which polycystic kidney is a one of the manifestations of the psiliopathy.

Scott Strothers: That everybody was using an antibody against SSD3 as a cytologic marker for immunostaining of the of the psiliopathy. So, SSD3 has expressed very cleanly in psiliopathy, and we know that the psiliopathy is that are caused by mutations in polycystins, which resulted in an imbalance of the cyclic AMP and calcium ratio in the psiliop, and also metastatic with too much cyclic AMP. And also metastatic analogs are acting, also metastatic receptors are acting to decrease cyclic AMP levels in cells, and in this case in the primary psiliopathy.

Scott Strothers: So, we'll be coming out with more and more data around this, but we've developed animal models in genetically engineered mice. We've done cyst models and dispersed kidney cells. We've done signaling. We've done a variety of things to begin to shore up the hypothesis that activating the SSD3 will be effective in polycystic kidney disease, but of course the real test is to get it into patients and see what it does. So, that's what we're trying to figure out how to get there, whether either ourselves or through partners, but a huge on met need, and just as a hint, you know, we don't expect based on the location in the renal tubules, that this will cause the type of very high urine volumes that you see with the phase of press and antagonists like 12 aptam. And that's one of the major limiting tolerability issues around the use of top aptam. Right. Well, thanks. Definitely looking forward to hearing more from that program in the future. Super exciting. Very high on met need.

Jonathan Wolleben: We'll take our next question from John Wallabin of Citizens JMP. Hey, good afternoon. Thanks for taking the question and that's wishes to mark.

Alan Krasner: Let's hope that you guys could talk a little bit about how you're thinking about next steps just simply in CAA, if you think you'd have enough information to move forward to a pivotal trial on how you think about integrating younger patients into the program as well. Well, thanks so much for the question. We have the full complement of patient data will definitely be able to talk to the FDA about the design of phase three.

Alan Krasner: So I think the data that you generate from those three cohorts in that trial will certainly be enough to go talk to the agency about our phase three design. And as far as the pediatric program, you know, we're also actively, you know, putting together for a protocol designs to evaluate that in phase two and then be able to use that, you know, to very quickly move into phase three. Because that obviously is a significant on medical need with the profound morbidity, you know, for those kids. So we're very, very focused on that. That's awful. Thank you very much.

Leland Gershell: I'll take our next question from Leland Gershell of Oppenheimer. Hey, good afternoon.

Scott Strothers: Thanks for taking my questions and Mark has been great working with you and best of luck in the future. Scott, why don't you ask on your thyro tropin receptor program you'd mentioned recent calls that you've been moving nicely along with potential candidates. Just wondering where you may be there. Could we see a clinical candidate nominated in the next few months or perhaps in .25. Thanks. Yeah, thanks, Leland. It's always hard to say when you're going to get there.

Scott Strothers: The process of drug discovery is very much an asymptote and you just keep getting closer and closer and closer to what you think is an ideal candidate. And a certain point you say that's good, that's good enough. And I got to say that in the TSH antagonist where one to 2% of the population can have this disease. And we just saw, I just saw the news this morning that one of my favorite characters Ray and Star Wars was just diagnosed with grave disease.

Scott Strothers: But this molecule needs to be really high quality. So we are working hard on that. I can tell we're really close. But whether that's this quarter, next quarter, early next year, I don't know for sure, but it's right around the corner. Great.

Jim Hazard: Thank you. We'll take our next question from Douglas Sal of HC Wainwright. Hi, good afternoon. Thanks for taking the questions. And I'll join the course of people saying how much we've enjoyed working with Mark over the years. I guess. You know, maybe a question for Jim, since he mentioned, you know, the fact that patients often have a very different experience of acramegly than clinicians realize. So I guess in terms of driving adoption, you know, how do you plan to get around that?

Jim Hazard: Because I think that has been a factor that has, you know, hamper, there was the launch of my caps, you know, in terms of converting that product. And I know that the, you know, how two students four files, very different on much much stronger data, but you know, just how do you promote from a tactical standpoint plan to address that aspect of the launch.

Jim Hazard: Thank you. Thanks Doug, and I think, you know, we'll all start where, where you've left off, which is, yeah, we've got a great product in Peltusatine. And that's something that does differentiate us certainly from most recent launches. But however, it is true that even with such a great product, what we hear from physicians is, if it's not broken, I'm not going to fix it. And that's exactly the purpose and the rationale behind our disease state campaign acramegly truth.com.

Jim Hazard: So already, you know, there's a small contingent of endocrinologist that are behind a lot of the data in this area of, again, trying to address this, this discord in dialogue. And it is really making sure that physicians are aware of the patient experience and then ensuring that, you know, as we get closer to launch that we really do empower patients to have that discussion with their endocrinologist based on the research that we've done.

Jim Hazard: Doug, it's a powerful message and I know that the physicians have reacted well to the awareness. And I will tell you that patients even react better to it when they see the campaign and realize that yes, this is the kind of discussion. These are the kinds of symptoms that they're feeling. This is what they want. This is the kind of discussion they want to have with their endocrinologist. So more to come and we'll be providing, you know, details as to, you know, how impactful this is and what the metrics are from the campaign. But it is really that the underpinning of a great product is the awareness around the problem. Okay, great. Thank you so much. And that's helpful. Thanks, Doug.

Corey Jubinville: And we'll take a question from Corey Juvenville of Lifestyle Capital. Hey, thanks for taking our questions and congrats on all the progress. And Mark congrats on everything you've helped build over the years.

Jim Hazard: We'll definitely be sad to see you go, but of course, wish you well and whatever comes next. But I guess can you help give us a bit of context in how your lawn shepherds in acromegly could potentially help support a launch in carcinoid syndrome down the line thinking about these prescriber groups is almost like a Venn diagram. How might a carcinoid patient, how often might a carcinoid patient be coming in contact with an endocrinologist that might have had previous experience with peltus teen treating acromegallics and, you know, while it's certainly been several errors ago.

Jim Hazard: Are there any learnings you're taking from the expansion of ox reattied or land reattied into these patient groups from acromegally to carcinoid syndrome or gap nets that can be applied to your strategy with peltus? Pizzuti. Thanks, Corey. We have already started to look at the overlap in terms of the customer base. And I'll tell you where we see a great deal of overlap is in the pituitary treatment centers. So the same academic centers, there are about 45 of these pituitary treatment centers.

Jim Hazard: And there is a good deal of overlap with, for example, the NCCN Cancer Network, the National Comprehensive Cancer Network. So places like Memorial Sloan Kettering, you know, Dr. Eliza Geer is at MSK, that's also obviously a cancer institution. And as well, to your point, there are, you know, specific endocrinologists that are very much involved in neuroendocrine tumors as well. So there is also an overlap. It will be though, you know, there's, it will be a new indication for us to get into and oncologists are going to be a new audience for us, but again, where they're located is a lot of co-location and in a great opportunity for us.

Jim Hazard: And maybe I'll just add to that, Corey, that beyond the actual practicing physicians and their staff, you know, launching your first drug is an exercise and building out a range of different capabilities, relationships with those institutions, the pharmacies of those institutions, relationships with the patients. And as I mentioned, just our internal capabilities. So there's the huge amount of synergy between this and then the second launch. And then that, of course, also support the third launch and fourth launches with AttumelNet. And then the many, many other launches we anticipate with other things coming out of the pipeline.

Unknown Executive: Excellent. Thank you for your questions. Thank you. And there are no further questions at this time.

Unknown Executive: I'd be happy to return the call to our hosts for any closing comments. Thank you all for being here and listening to us. And those of you who have such affection for Mark, he's not going anywhere right away and you know how to find him. And I'm sure you'd be happy to have a drink and launch your ice cream and catch up sometime. Thank you all for listening.

This does conclude today's Kinetics Pharmaceuticals, second quarter, 2024 earnings conference call. Thank you for participating. You may now disconnect your line and have a great day. Thank you. [inaudible]