Q1 2024 BioAtla Inc Earnings Call
Operator: Greetings and welcome to the Bioatla first quarter 2024 earnings call. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Bruce Mackle, with Lifescyte Advisors. Thank you, Bruce. You may begin.
Greetings and welcome to the bio Atlas first quarter 'twenty 'twenty four earnings call. At this time all participants are in a listen only mode. A brief question and answer session will follow the formal presentation.
Operator: They want to require operator assistance during the conference. Please press star zero on your telephone keypad.
Operator: As a reminder, this conference is being recorded it is now my pleasure to introduce your host Bruce Mackle with lifestyle advisors. Thank you Bruce you may begin.
Operator: Yes.
Bruce Mackle: Thank you, operator, and good afternoon everyone. With me today on the phone from Bioatla are Dr. Jay Short, Chairman, CEO, and Co-Founder, Dr. Eric Sievers, Chief Medical Officer, Sheri Lydick, Chief Commercial Officer, and Richard Waldron, Chief Financial Officer. Following today's call, the team will participate in a short Q&A. Earlier this afternoon, Bioatla released financial results and a business update for the first quarter ended March 31st, 2024. A copy of that press release and corporate presentation is available on the company's website.
Thank you operator, and good afternoon, everyone with me today on the phone from bio outline our Doctor Jay short Chairman CEO and co founder Dr. Eric Sievers, Chief Medical Officer.
Operator: Sherri Leidig, Chief commercial officer, and Richard Waldron, Chief Financial Officer.
Team: Following today's call the team will participate in a short Q&A.
Team: Earlier this afternoon bio outlet released financial results and a business update for the first quarter ended March 31st 2024.
Team: A copy of that press release and corporate presentation are available on the company's website.
Bruce Mackle: Before we begin, I'd like to remind everyone that statements made during this conference call will include forward-looking statements, including, but not limited to, statements regarding Bioatla's business plans and prospects and whether its clinical trials will support registration, Plans to form collaborations and other strategic partnerships for selected assets, and achievement of milestones.
Sheri Lydick: Before we begin I'd like to remind everyone that statements made during this conference call will include forward looking statements.
Sheri Lydick: Including but not limited to stay.
Bio Atlas: Statements regarding bio Atlas business plans and prospects and whether its clinical trials will support registration.
Company Representative: Plans to form collaborations and other strategic partnerships for selected assets.
Company Representative: The achievements of milestones.
Bruce Mackle: Results, Conduct, Progress, and Timing of its Research and Development Programs and Clinical Trials, as well as expectations with respect to enrollment and dosing in its clinical trials. Plans and Expectations Regarding Future Data Updates, Clinical Trials, Regulatory Meetings, and Regulatory Submissions; The Potential Regulatory Approval Path for its Product Candidates, Expectations about the Sufficiency of its Cash and Cash Equivalents to Fund Operations, and Expectations regarding R&D expenses and cash flow. These statements are subject to various risks, assumptions, and uncertainties that can cause actual results to differ materially and are described in the filings made with the SEC, including the most recent quarterly report on Form 10-Q.
Company Representative: Results conduct progress and timing of its research and development programs and clinical trials.
Company Representative: The expectations with respect to enrollment and dosing in its clinical trials.
Company Representative: Plans and expectations regarding future data updates clinical trials regulatory meetings and regulatory submissions.
Company Representative: Potential regulatory approval path for its product candidates the expectations about the sufficiency of its cash and cash equivalents to fund operations.
Speaker Change: And expectations regarding R&D expenses and cash burn.
Speaker Change: These statements are subject to various risks assumptions and uncertainties that can cause actual results to differ materially and are described in our filings made with the S. E C, including the most recent quarterly report on Form 10-Q.
Bruce Mackle: You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, May 14, 2024, and Bioatla disclaims any obligation to update such statements to reflect future information, events, or circumstances, except as required by law. With that, I'd like to turn the call over to Jay Short. Jay?
bio attalid: You are cautioned not to place undue reliance on these forward looking statements, which speak only as of today may 14th 2024, and bio attalid disclaims any obligation to update such statements to reflect future information events or circumstances, except as required.
bio attalid: Mired by law.
bio attalid: With that I'd like to turn the call over to Jay short.
bio attalid: Jay.
Jay M. Short: Thank you, Bruce, and thanks to everyone for joining us for our first quarter 2024 Bioatla earnings call. Additional details related to what we will share today are available in today's press release and our updated company presentation, both of which are available on our website.
Jay M. Short: Thank you Bruce and thanks to everyone for joining us for our first quarter 'twenty 'twenty four blah Blah Blah earnings call additional details related to what we will share today are available in today's press release, and our updated company presentation, both of which are available on our website.
Jay M. Short: We continue to make considerable progress across all of our ongoing clinical programs. We are pleased to share our recent encouraging data readouts for our CAVOR2 ADC and highly treatment-refractory head and neck cancer patients who had a median of three prior lines of treatment. As illustrated in the best overall response slide of our corporate presentation, many patients achieved rapid and deep tumor control, with 38% of patients responding. Having observed an 86% disease control rate, we believe these findings support use in earlier line settings.
Jay M. Short: We continue to make considerable progress across all of our ongoing clinical programs. We are pleased to share. Our recent encouraging data read outs for a cab or two ADC is highly treatment refractory head and neck cancer patients who had a median of three prior lines of treatment.
Jay M. Short: As illustrated in the best overall response flight of our corporate presentation, many patients achieved rapid and deep tumor control with 38% of patients responding.
Speaker Change: Having observed an 86% disease control rate. We believe these findings support used in earlier line settings.
Jay M. Short: In addition, in view of the manageable safety profile, this holds considerable promise for future combination therapy. Given the strength of the data we observed with CAB or 280C, especially at the more intensive 2Q3W dosing regimen, we plan to meet with the FDA in the second half of this year for guidance on a potentially registrational trial. We obtained multiple responses and encouraging clinical benefit using the less intense Q2W dose of our CAVOR 280C and melanoma. However, we did not meet our internal bar.
Speaker Change: In addition in view of the manageable safety profile. This holds considerable promise for future combination therapies.
Speaker Change: Given the strength of the data, we observed with cab or to a D C, especially at the more until it seems to Q3 W. Dosing regimens, we plan to meet with the S. T. A N. The second half of this year for guidance of a potentially registrational trials.
Speaker Change: We obtained multiple responses and encouraging clinical use.
Speaker Change: Using the less intense Q2 W dose of a cab or to maybe see in melanoma.
Speaker Change: However, we did not meet our internal bar, we do believe though that our cab or to a D. C. At the more intensive regimen has potential in melanoma and other indications, including triple negative breast cancer, where we observed tumor reduction in our earlier phase one study.
Jay M. Short: We do believe, though, that our CAVOR2 ADC at the more intensive regimen has potential in melanoma and other indications, including triple negative breast cancer, where we observed tumor reduction in our earlier phase one study. However, due to our ongoing prioritization, we do not plan to explore the more intensive regimen at this time. Next, I will cover our ongoing Phase 1-2 trial with our CAB CTLA-4-IO antibody. A Phase 1 study which was expanded to a higher dose due to the encouraging safety results is progressing well. We've more than doubled the number of treated patients since our first data disclosure late last year.
Company Representative: However, due to our ongoing prioritization you do not plan to explore the more intensive regimen at this too.
Speaker Change: Next I will cover our ongoing phase one two trial with our Caf seats L. A for I O antibody.
Speaker Change: Our phase one study, which was expanded to a higher dose due to the encouraging safety results is progressing well.
Speaker Change: We've more than doubled the number of treated patients since our first data disclosure late last year and we have observed multiple responses at the 350 milligram dose in combination with PD one.
Jay M. Short: And we have observed multiple responses at the 350 milligram dose in combination with PD-1. We are pleased to report that our ongoing Phase 2 study echoes our earlier report, as very few immune-related adverse events have been observed to date, which is consistent with the anticipated benefits of our conditional binding technology. In addition, the observed safety profile also continues to hold now that we are treating patients at the 700 milligram flat dose, or approximately 10 milligrams per kilogram.
Speaker Change: We are pleased to report that our ongoing phase two study echoes. Our early report is very few immune related adverse events have been observed to date, which is consistent with the anticipated benefits of our conditional binding technology.
Speaker Change: In addition, the observed safety profile also continues to hold now that we are treating patients at the 700 milligrams flat dose were approximately 10 milligram per kilogram.
Jay M. Short: We also remain on track to clear the DLP observation period with the unprecedented one gram dose later this quarter. The manageable safety at this high dose allows us to approach the maximum activity for a CTLA-4 inhibitor in the tumor, which has not previously been achieved in the past. As for our CAV-AXL-ADC, we completed dosing patients in the first portion of our potentially registrational trial in undifferentiated pleomorphic sarcoma in April. We also remain on track to evaluate clinical benefits of the AXL-ADC in target agnostic cancer patients later this quarter.
Speaker Change: We also remain on track to clear the D. L. T observation period with the unprecedented one gram dose later this quarter.
Speaker Change: The manageable safety at this high dose allows us to approach the maximum activity for a cta for inhibitor in the tumor which has not previously been achieved in the clinic.
Speaker Change: As for our Capex. The ADC, we completed dosing of patients in the first portion of a potentially registrational trial in undifferentiated pleomorphic sarcoma in April.
Ignostic: We also remain on track to evaluate clinical benefit of the axle ADC target Ignostic cancer patients later this quarter.
Jay M. Short: Finally, the phase one dose escalation trial with our first dual-CAB-Bi-specific EPCAM CD3 T-cell engager remains on track for readout in the second half of this year. As we are now into the second quarter of 2024, we are focused on finalizing data readouts and reports for our Ward 2 and C24 assets for meetings with the FDA to obtain guidance on one or more potentially registrational trials in the second half of this In addition, we are advancing our discussions with potential pharmaceutical partners on selected preclinical and clinical assets to both accelerate their development and maximize their market potential. I will now turn the call over to Eric, who will provide additional insights and details on our Ward 2 and CTOA-4 assets. Eric?
Speaker Change: Finally, the phase one dose escalation trial with our first dual cab by specific F. Cam C. D. Three T cell engaging remains on track for readout in the second half.
Speaker Change: As we are now into the second quarter of 'twenty 'twenty. Four we are focused on finalizing data read outs and reports for our war to let's see it's only four assets for meetings with the F. D. A to obtain guidance on one or more potentially registrational trials in the second half of this year. In addition, we are advancing our discussions with potential pharma.
Speaker Change: Suitable partners on selected preclinical and clinical assets to both accelerate their development and maximize their market potential.
Eric: I will now turn the call over to Eric who will provide additional insights and details on our war to let's see till a four assets Eric.
Eric L. Sievers: Thank you, Jay. Beginning with our CAB ROR2-ADC, Ozariftamab-Vadotin, in the target agnostic head and neck cancer indication, we have enrolled a total of 33 patients who had a median of three prior treatments, ranging from one to six prior lines of treatment. 21 received more intensive day one and eight dosing in three-week cycles, and 12 received every other week dosing. Among the 29 who were evaluable for response assessment, 11 responses were documented, and five responses are now confirmed to date.
Eric Smith: Thank you Jay beginning with our cab roared to a D C pose a risk to map the dosing and the target agnostic head and neck cancer indication. We have enrolled a total of 33 patients who had a median of three prior treatment regimens ranging from one to six.
Eric L. Sievers: Notably, four of five confirmed responses occurred in patients who received the ADC as second or third line therapy. Further follow-up will be required to provide a reliable estimate of the response duration. Importantly, responses were observed regardless of ROR2 target expression from pretreatment tumor biopsies evaluated by immunohistochemistry. As of the safety data cut in March, only one patient discontinued treatment due to a treatment-related adverse event, which was peripheral neuropathy. Collectively, these data support advancing to earlier lines of therapy, potentially in combination with PD-1 inhibition in the first-line setting.
Eric Smith: Prior lines of treatment.
Eric Smith: 'twenty one received more intensive day, one in eight dosing in three week cycles and 12 received every other week dosing.
Eric Smith: Among the 29, who were Evaluable for response assessment 11 responses were documented and five responses are now confirmed today.
Notably: Notably four of five confirmed responses occurred in patients who received the ADC as second or third line therapy.
Eric Smith: Further follow up will be required to provide a reliable estimate that the response duration.
Speaker Change: Importantly responses were observed regardless of where to target expression from pretreatment tumor biopsies evaluated by immunohistochemistry.
Speaker Change: As if the safety data cut in March only one patient discontinued treatment due to a treatment related adverse event, which was peripheral neuropathy.
Speaker Change: Collectively these data support advancing to earlier lines of therapy.
Speaker Change: Essentially in combination with PD, one inhibition in the first line setting.
Eric L. Sievers: A meeting with the FDA is anticipated in the second half of the year to discuss potential registrational trial approaches. Moving now to our CAB CTLA-4 antibody, evalstatone. Over the past 25 years, multiple lines of clinical evidence have shown that increased exposure of CTLA-4 blockade in combination with PD-1 inhibition drives long-term survival benefits. At the same time, most oncologists prescribe.
Speaker Change: A meeting with the FDA is anticipated in the second half of the year to discuss potential Registrational trial approaches.
FDA: Moving now to our cab see Chile, four antibody E valves to attack.
FDA: Over the past 25 years in multiple lines of clinical evidence have shown that increased exposure of <unk> four blockade in combination with PD, one inhibition drives long term survival benefits at.
Speaker Change: At the same time, most oncologists prescribed.
Eric L. Sievers: Currently, approved CTLA-4 blocking antibodies are at relatively low doses because a high rate of immune-related adverse events limit tolerability. We designed valstatug to preferentially bind CTLA-4 in the acidic tumor microenvironment to avoid binding in normal healthy tissues and lymph nodes. We believe valstatug will be better tolerated, enabling more patients to receive clinical benefit from CTLA-4 inhibition. Last quarter, we announced confirmed responses in two of six treatment-refractory patients using the 350 milligram dose in combination with PD-1 antibody.
Speaker Change: Currently approved see till April or blocking antibodies at relatively low doses because of high rates of immune related adverse events limit tolerability.
Valdosta: We designed at Valdosta type to preferentially binds secretly for in the aesthetic tumor microenvironment to avoid binding and normal healthy tissues and lymph nodes.
Speaker Change: We believe that <unk> will be better tolerated and.
Speaker Change: Enabling more patients to receive clinical benefit from <unk> inhibition.
Speaker Change: Last quarter, we announced confirmed responses.
Valdosta: For two of six treatment refractory patients using the 350 milligram dose in combination with PD one antibody.
Eric L. Sievers: As part of today's update, another response has now been achieved in a melanoma patient whose Evalstatug dose was increased from 70 mg to 350 mg given every three weeks, providing additional evidence that higher doses drive clinical benefit. As Jay mentioned, patients are tolerating the unprecedented one-gram dose level that we are presently evaluating as part of our continued dose escalation. We continue to enroll in the Phase 2, first-line melanoma and non-small cell lung cancer combination cohorts at the 700 milligram flat dose.
Speaker Change: As part of today's update another response has now been achieved in a melanoma patient, whose <unk> dose was increased from 70 milligrams to 350 milligrams. Given every three weeks, providing additional evidence that higher doses drive clinical benefit.
Jane: As Jane mentioned patients are tolerating the unprecedented one gram dose level that we are presently evaluating as a part of our continued dose escalation.
Jane: We continue to enroll in the phase III first line melanoma and non small cell lung cancer combination cohorts at the 700 milligrams flat dose.
Eric L. Sievers: We are on track for additional data readouts later this year, and investigators are enthusiastic about using a CPLA-4 inhibitor at higher doses in highly treatment-refractory cancer patients. And we will report a Phase 1 update at ASCO on June 1st, shifting to our registration plan.
Speaker Change: We are on track for additional data Readouts later this year <unk>.
Investigators: Investigators are enthusiastic to use a <unk> four inhibitor at higher doses and highly treatment refractory cancer patients and we will report phase one update at ESCO.
Investigators: June 1st.
Speaker Change: Shifting toward registration plans, we are now focused on the marked unmet need.
Sheri Lydick: We are now focused on the marked unmet need among patients with newly diagnosed metastatic or unresectable BRAF-mutated melanoma, who account for approximately half of patients with melanoma. Our strategy is informed by three key findings from large prospective clinical trials. First, BRAF patients should receive checkpoint inhibitor treatment before BRAF inhibitor therapy. Second, combined use of CTLA-4 and PD-1 blockade helps drive both progression-free and overall survival. Third, higher CTLA-4 doses meaningfully and specifically improve overall survival.
Speaker Change: Patients with newly diagnosed metastatic or unresectable.
Speaker Change: BRAF mutated melanoma will account for approximately half of patients with melanoma.
Speaker Change: Our strategy is informed by three key findings from large prospective clinical trials first BRAF patients should receive checkpoint inhibitor treatment before BRAF inhibitors second combined use of <unk> four and PD, one blockade helps drive both progression free.
Speaker Change: And overall survival.
Speaker Change: Third higher CTO laid four doses meaningfully specifically improve overall survival.
Sheri Lydick: Notably, improved progression-free survival for this patient subgroup first appeared at just three months, suggesting that adding Cpla-4 inhibition quickly achieves tumor control for these BRAF melanoma patients. We believe that our conditionally binding CTLA-4 antibody can safely achieve high, unprecedented levels of CTLA-4 blockade in the tumor microenvironment, while largely avoiding CTLA-4 inhibition in normal tissue. We are now designing an efficient, blinded, randomized, pivotal trial employing evalstatug plus pembrolizumab for newly diagnosed patients with BRAF-mutated metastatic or unresectable melanoma.
Speaker Change: Notably improved progression free survival for this patient subgroup first appeared at just three months.
Speaker Change: Adjusting that adding stipulate for inhibition quickly achieved tumor control these BRAF melanoma patients.
Speaker Change: We believe that our conditionally binding, particularly for antibody can safely achieve high unprecedented levels of C. T. L. A for a blockade in the tumor microenvironment, while largely avoiding seat to lay four inhibition in normal tissues.
We: We're now designing an efficient blinded randomized pivotal trial, employing if alphatec plus pembina as a mad for newly diagnosed patients with BRAF mutated metastatic or unresectable melanoma.
Sheri Lydick: We anticipate FDA feedback in the second half of this year, positioning us to initiate the potentially registrational trial by year's end. I would now like to turn the call over to Sheri to provide a few comments on the market opportunities for these agents. Sheri?
We: We anticipate F D. A feedback in the second half of this year positioning us to initiate the potentially registrational trial by years end.
We: I'd now like to turn the call over to Sherry to provide a few comments on the market opportunities for these agents sure.
Sheri Lydick: Thank you, Eric, and good afternoon, everyone. Continuing with our CAB CTLA-4 antibody, Avastatug. Based on our evolving phase one data, we continue to believe Avastatug has the potential to be a best-in-class CTLA-4 inhibitor that holds the promise to be used often as a PD-1 inhibitor and potentially expand the indications where combined immune checkpoint inhibition can be used. There is tremendous opportunity across many solid tumors for Rivalstutok, but we are focused initially on BRAF mutated metastatic melanoma as a potential efficient path to approval with a high likelihood of success.
Sherry: Thank you Eric and good afternoon, everyone continuing with our current C. P. R H score antibody announced attack.
Sherry: Based on our evolving phase one data we continue to believe I've asked the park has the potential to be best in class C. P. R. A swag that hurts. The promised three years, just often as a PD one inhibitor.
Eric Smith: Essentially expand the indications where combined immune checkpoint inhibition can be effective.
Speaker Change: There is tremendous opportunity across many solid tumors to bring about the park, but we are focused initially on B RAF mutated metastatic melanoma as a potential efficient path joked about it the high likelihood of success.
Sheri Lydick: The current worldwide therapeutic market size of metastatic melanoma is approximately 8 billion annually and is expected to grow to over 11 billion by 2028. BRAF mutations are present in approximately 50% of malignant melanoma patients, and the first-line standard of care remains immunotherapy regardless of BRAF status.
Speaker Change: Worldwide therapeutic market price with metastatic melanoma is approximately 8 billion annually and is expected to grow that you're over 11 billion by 2028.
Speaker Change: BRAF mutations are present in approximately 50%.
Speaker Change: None of the patients in first line standard of care.
Speaker Change: Immunotherapy, regardless of BRAF status.
Sheri Lydick: As Eric noted earlier, documented clinical benefits of adding an anti-CTLA-4 antibody to a PD-1 inhibitor are particularly striking in BRAF-mutated patients, and we believe that the combination of Velstatub with a PD-1 inhibitor has the potential to become the standard of care for these patients. Next, we turn to our CABOR II ADC, ozotriptimazidose.
Eric Smith: As Eric noted earlier documented clinical benefits of adding <unk>.
Eric Smith: T jewelry flash or a PD, one inhibitor I, particularly striking in BRAF mutated patients.
Eric Smith: And we believe that the combination of analysis, because like a PD one inhibitor has the potential to become the standard of care for these patients.
Cadbury: Onto our Cadbury two ADC unless you recognized.
Sheri Lydick: We are encouraged by the single agent clinical profile that is emerging in multi-refractory, heavily pre-treated head and neck cancer. The worldwide prevalence and mortality rate for this population are significant, and despite recent advances, there remains a profound unmet need, particularly for patients who have progressed on first-line treatment options. Therapies available to these refractory patients are limited and have suboptimal clinical benefits.
Eric Smith: We are encouraged with the single agent clinical profile that is emerging and multi refractory heavily pretreated had an absolutely does.
unknown: Worldwide prevalence and mortality rate for this population are significant and despite recent advances there remains a profound unmet need particularly for patients who have progressed on first line treatment option.
Speaker Change: Therapies available for these refractory patients are limited and have suboptimal clinical benefit.
Sheri Lydick: The current worldwide therapeutic market size for head and neck cancer is approximately $3.5 billion annually and is expected to grow significantly to nearly $5 billion over the next five years. Given the encouraging emerging data set for head and neck cancer, we believe ozoriptomab vidotin could represent a significant commercial opportunity for Bioatla. We also believe Ozarictumab-Bidotin is well positioned for a strategic collaboration that will expand the potential of this CAB-ADC across multiple solid tumor indications.
unknown: The current real life therapeutic market size of head and neck cancer is approximately $3 5 billion annually.
unknown: It is expected to grow significantly to nearly 5 billion over the next five years.
unknown: Given the encouraging emerging dataset and head and neck cancer, we believe the retina.
Speaker Change: Could represent a significant commercial opportunity for <unk>.
unknown: We also believe the retina, but don't it's about congestion first strategic collaboration that will expand the potential I guess CAD 80 feet across multiple solid tumor indications.
Sheri Lydick: Given the combined prevalence of head and neck cancer and BRAF-mutated melanoma, we believe these assets and indications represent potentially meaningful, value-creating opportunities for Bioatla with the potential to redefine the standard of care for patients with these devastating diseases. With that, I would now like to turn the call back over to Jay.
bio <unk>: Given the combined prevalence of head and neck cancer and BRAF mutated melanoma, we believe these assets and indications represent potentially meaningful value, creating opportunities for bio <unk> with the potential to redefine standard of care for patients with these devastating diseases.
Jay: With that I would now like to turn the call back over to Jay.
Jay: Thank you Sherry.
Jay M. Short: Next, a few words about our potentially first-in-class dual-CAB, bispecific T-cell-engager antibody, CAB EpKim, and CAB CD3. EPCAM is a ubiquitous target expressed on the surface of cancer cells, which requires the use of our CAB technology to achieve optimal selectivity and safety. We are on track to report the full data set from the Phase I study in the second half of this year, with a potential Phase II study initiating also in the second half of this year.
Jay: Next a few words on our potentially first in class dual cab Bispecific T cell engaging antibody cab F. Chem cab C D. Three.
Jay: Cam is a ubiquitous target expressed on the surface of cancer cells, which requires the use of a cab technology to achieve optimal selectivity is safety.
Speaker Change: We are on track to report the full data set from the phase one study in the second half of this year with a potential phase two study initiating also in the second half of this year.
Jay M. Short: The T-Cell Engager space offers tremendous opportunity for more effective therapies, and in particular, our CAB-enabled Epcan T-Cell Engager has the potential to treat patients with a wide range of metastatic tumors, including cancers of the colon, lung, breast, pancreas, and prostate, among others. Bioatla has developed a novel next-gen carbohydrate linker system to further reduce the potential risks associated with neutr This ADC has the potential for broad applicability, including for new indications such as pancreatic cancer.
F. Chem: The T cell engagement space offers tremendous opportunity for more effective therapies that are particular, our cab enabled F. Chem T cell engage your has the potential to treat patients with a wide range of metastatic tumors, including cancers colon lung breast pancreas and prostate among others.
Unknown Speaker: <unk> has developed a novel Nextgen carbohydrate linker system to further reduce the potential risks associated with neutropenia from off target toxicity used in a cab becton for ATC.
Purdue: This ADC has the potential for broad applicability, including Purdue indications such as pancreatic cancer.
Jay M. Short: We recently presented compelling anti-tumor activity, PK, and toxicology data last month at the AACR annual meeting that indicate CABNIC and 4-ADC is potentially a more effective treatment with reduced toxicity. As part of today's update, we have received FDA IND clearance for this agent and are evaluating several options as we continue to focus our resources on our later stage clinical program. With that, I would now like to turn the call over to Rick to review the first quarter of 2024 financials. Rick.
Purdue: We recently presented compelling anti tumor activity PK and toxicology data last month at the ACR annual meeting that indicate cabinet good for a D C as potentially a more effective treatment.
Speaker Change: With reduced toxicity.
Rick: As part of today's update we have received FDA I. Indeed clearance for this agent and are evaluating several options as we continue to focus our resources on our later stage clinical programs with that I would now like to turn the call over to Rick to review the first quarter 'twenty 'twenty four financials Rick.
Rick Smith: Thank you Jay reset.
Richard A. Waldron: Research and development expenses were $18.9 million for the quarter ended March 31, 2024, compared to $21.7 million for the same quarter in 2023. The decrease of $2.8 million was primarily due to completion of preclinical development related to our Nectin IV IND and prioritization of our clinical programs in 2023. We expect our R&D expenses to continue to decrease in the near term due to recently completed enrollment in clinical trials for data sets expected to enable potentially registrational trials for our ADC program.
Rick Smith: Research and development expenses were $18 $9 million for the quarter ended March 31, 2024, compared to $21 7 million for the same quarter in 2023.
Rick Smith: The decrease of $2 $8 million was primarily due to completion of preclinical development related to our neck in for I N D and prioritization of our clinical program in 'twenty two 'twenty three.
Speaker Change: We expect our R&D expenses to continue to decrease in the near term due to recently completed enrollment in clinical trials for datasets expected to enable potentially registrational trials for our a D C program.
Rick Smith: Okay.
Richard A. Waldron: General and administrative expenses were 5.6 million dollars for the quarter ended March 31, 2024, compared to 7.2 million dollars for the same quarter in 2023. The $1.6 million decrease was primarily due to lower stock-based compensation and professional fees. The net loss for the quarter ended March 31, 2024 was $23.2 million compared to a net loss of $27.4 million for the same quarter in 2023. Cash and Cash Equivalents as of March 31, 2024 were $80.6 million compared to $111.5 million as of December 31, 2023.
Speaker Change: General and administrative expenses of about $5 $6 million for the quarter ended March 31, 2024 compared to $7.2 million for the same quarter in 2023.
Speaker Change: The $1.6 million decrease was primarily due to lower stock based compensation and professional fees.
Speaker Change: Net loss for the quarter ended March 31, 'twenty 'twenty.
Speaker Change: Paul was $23.2 million compared to a net loss of $27 $4 million, but at the same quarter in 2023.
Speaker Change: Cash and cash equivalents as of March 31, 2024.
Speaker Change: Were $86 million compared to $111.5 million as of December 31, 2023.
Richard A. Waldron: Net cash used in operating activities for the quarter ended March 31, 2024 was $30.8 million compared to net cash used in operating activities of $22.7 million for the same period in 2023. Our cash use for the quarter ended March 31, 2024 included approximately $5 million in annual payments that typically occur during our first fiscal quarter. We expect our operating cash burn to be approximately $20 million for the quarter ending June 30, 2024 and to continue to decrease in the second half of the year as we complete treatments in our ADC clinical trials, allowing our current cash and cash equivalents to fund operations into the second half of 2025.
Speaker Change: Net cash used in operating activities for the quarter ended March 31, 2024 was $38 million compared to net cash used in operating activities of $22.7 million for the same period in 2023.
Speaker Change: Yeah.
Speaker Change: Our cash used for the quarter ended March 31, 'twenty 'twenty four included approximately $5 million in annual payments that typically occur during our first fiscal quarter.
Speaker Change: We expect our operating cash burn to be approximately $20 million for the quarter ending June 30, 'twenty 'twenty four and took to continue to decrease in the second half of the year as we complete treatment in our ADC clinical trials, allowing a cat current cash.
Speaker Change: And cash equivalents to fund operations into the second half of 2025.
Jay: And now back to Jay.
Jay: Thank you Rick.
Jay M. Short: We are pleased with the considerable progress we have made to date and our cumulative results across our CAB pipeline targeting solid tumors. We look forward to multiple important milestones this year, including several planned meetings with the FDA to discuss a potentially registrational trial with Ward 2 in head and neck cancer. Guidance on the remaining portion of the registrational trial in UPS with Axel and Guidance for a Potentially Registrational Trial with CTLA-4 in BRAF Mutated Melanin. With that, we will turn it back to our operator to take your questions. Thank you.
Jay: We are pleased with the considerable progress we have made to date and our cumulative results across our cab pipeline targeting solid tumors.
Jay: We look forward to the multiple important milestones this year, including several planned meetings with the FDA to discuss a potentially registrational trial with <unk> two in the neck cancer.
Jay: Guidance on the remaining portion of the Registrational trial in U P S with Axel.
Axel: And guidance for a potentially registrational trial with <unk> four in BRAF mutated melanoma.
Operator: With that we will turn it back to our operator to take your questions.
Operator: Thank you. We'll now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.
Operator: Thank you well now be conducting a question and answer session. If you'd like to ask a question. Please press star one on your telephone keypad and confirmation tone will indicate your line is in the question queue.
Operator: Press Star two if you'd like to remove your question from the queue for participants using speaker equipment. It may be necessary to pick up your handset before pressing the sarkies my mom in place, while we poll for questions.
Operator: One moment, please, while we poll for questions. Thank you. Our first question is from Brian Cheng with JPMorgan. Please proceed with your question.
Operator: Thank you. Our first question is from Brian Cheng with J P. Morgan. Please proceed with your question.
Brian Chan: Hey guys, thanks for taking our question this afternoon. Um, can you elaborate on the duration of the confirmed responses that you're seeing with your raw 2ADC in head and neck today? And what is your expectation of the duration of responses as the dataset matures?
Brian Cheng: Hey, guys. Thanks for taking my question this afternoon.
Brian Cheng: Can you elaborate on the duration of that confirmed responses that youre seeing with euro to a D C in head and neck today.
Operator: And what is your expectation on Detroit duration of response as the D S that mature.
Operator: Yeah.
Jay M. Short: Thanks, Brian. I'll let Eric take a crack at this one. Thank you.
Operator: Thanks, Brian Oh, Eric I'll take a crack at this one thank you.
Eric L. Sievers: Thanks, Brian. So we definitely need further follow-up to estimate our duration of response, but I will refer you to slide 29 of our updated corporate deck. The swimmers plot gives you a sense of the confirmed responses and addresses the question you asked, particularly the patients that were treated at every other week dosing. I will note that those patients were dosed first, and then after completing that effort, we then went on to employ the days one and eight regimen. So we have a bit longer follow-up for the patients in blue on slide 29.
Brian Cheng: Thanks, Brian.
Eric Smith: So we definitely need further a follow up test to meet our duration of response, but I will refer you to slide 29 of our updated corporate deck.
Eric Smith: The swimmers plot gives you a sense of the confirmed responses and addresses. The question you asked I am particularly that the patients that were treated at the every other week dosing.
Speaker Change: You'll note that those patients are where.
Speaker Change: We're dose first and then after completing that effort. We then went on to employ that days, one and eight regimen. So we have a bit longer follow up for the patients in blue on slide 29.
Eric L. Sievers: And I'll just add there are eight patients still on treatment and that are ongoing, of which two have responses that could confirm, and there are also two with decreasing tumor volume.
Speaker Change: And I'll just add a there are.
Speaker Change: Eight patients still on treatment and that.
Speaker Change: That are ongoing are which to have.
Speaker Change: [noise] responses that could confirm and Theres also too with a decreasing tumor volume.
Eric L. Sievers: Great, and then maybe you can help us also frame the expectation of response level and also the duration of response with the current standard of care in head and neck today, in you know, second line and also third line [inaudible]
Speaker Change: Great and then maybe can you help us also frame the expectation of a response level and also the duration of bonds with the current standard of care in head and neck today in second line and also a third line.
Eric L. Sievers: Yeah, so when you look at the later lines, we're thinking, you know, if you could get four months plus in these, you know, keep in mind, we're fourth line here, three prior lines, median three prior lines. So this is really out there. The bar is exceptionally low, especially when you look at the second line, where you're getting on from a response rate standpoint, 13% on average. And so there you would like to see, you know, I think five months plus, obviously, go to first line; you'd like to see half a year plus. But I think given the late lines we're in, I think that it's encouraging.
Speaker Change: Yeah, you bet.
Speaker Change: So I think when you look at the later lines were thinking if you could get four months plus the lease.
Speaker Change: Keep in mind, we're fourth line here three prior lot of median three prior lines. So this is really out there.
Speaker Change: The bar is exceptionally low, especially when you look at second line, where you are getting on a from a response rate standpoint, a 13% below the average and so there you would like to see you know I think five months plus obviously you got a first line you'd like to see it half a year plus but I think given the late lines. We're in.
Speaker Change: I think that it's encouraging.
Speaker Change: Great. Thank you so much.
Speaker Change: Yeah.
Dingding Shi: Thank you. Our next question is from Kelly Shi with Jeffries. Please proceed with your question.
Kelly <unk>: Thank you. Our next question is from Kelly <unk> with Jefferies. Please proceed with your question.
Dingding Shi: Hi, everyone. Thank you. Thank you for taking our question. This is Dev from Kailishi, and congratulations on the progress. I have a couple of questions on AXL.
Dave: Hi, everyone. Thank you. Thank you for taking a question this is Dave on color.
Dave Color: And congratulations on the progress I have couple of question on EXL can.
Dave: Can you provide any color on a median follow up that you might need before you'll need to death.
Dave Color: And second half and also do you expect to start the next stage of recouping in 2024 or it could be in early 'twenty.
Dave Color: Thank you.
Dev Prasad: Can you provide any color on median follow-up that you might need before you meet with the FDA in the second half? And also, do you expect to start the next stage of recruiting in 2024? Or could it be in early 2025?
Speaker Change: Thank you, yeah, where because we have completed the dosing that we intended for the first portion of the potentially Registrational trial.
Jay M. Short: Thank you. Yeah, because we've completed the dosing that we intended for the first portion of the potentially registrational trial, our main goal here is to achieve multiple scans for each of those patients, which we think should readily occur in the second half of this year. And so, our current thinking, assuming we continue to get encouraging data, is that we would have an opportunity to start that next portion of the remaining portion of the registrational trial in late 2024.
Speaker Change #103: Main goal here is to achieve multiple scans for each of those patients, which we think should readily occur in the second half of this year and so our current thinking assuming we got encouraging continue to get encouraging data that we would have an opportunity to start that's a next portion of the ore.
Speaker Change #102: <unk> portion of the Registrational trial.
Speaker Change: In 'twenty late 'twenty 'twenty four.
Jay M. Short: and one more on non-small cell lung cancer and my phase 3 trial. Can you remind me whether you started those trials in second line or third line, or do you need any more alignment with the FDA?
Speaker Change #100: And one more on the non small cell lung cancer randomized phase III trial.
Speaker Change #105: Can you remind me did you started those trial in second line or Thailand, or do you need any more alignment with DST.
Jay M. Short: Well, in the non-small cell lung cancer, there was, if I recall correctly, a median of three prior lines there, so it was pretty late, very refractory patients. And, you know, we reported that out in December of last year, and we've done an extension to that study to look at target agnostic patients. So we'll have that data still later this quarter, and we're going to pick an appropriate way to communicate that data once we get to the end of this quarter.
Speaker Change #100: Well.
Speaker Change #101: On the non small cell lung cancer.
Speaker Change: If I recall correctly, a median of three prior lives there. So it was pretty late.
Speaker Change #107: Refractory patients.
Speaker Change #109: And you know we reported that out in December of last year.
Speaker Change: And we've done that.
Speaker Change #104: An extension to that study to look at the target agnostic patients. So we'll gifts, where we'll have that data in a still late later this quarter and we're going to pick out an appropriate way to communicate that data once we get to the end of this quarter and so and then I think from there.
Jay M. Short: And then from there, I think we've already got feedback from the FDA on how to proceed if one goes into a second line or a third line, which obviously is earlier than what our data comes from. So we feel that with that final data, we'll be well-positioned to lay out the final strategy for that, either independently or with partners.
Speaker Change #114: I think we've already got feedback from the F. D. A on how to proceed if one goes into a second line or third line, which obviously is earlier than what we our data comes from so we feel that with that final data will be well positioned to Oh lay out the final strategy for that.
Speaker Change #112: Either independently or with partners.
Jay M. Short: Okay, thank you. Thanks for taking our question.
Speaker Change #108: Okay. Thank you thanks for taking a question.
Operator: Thank you. Our next question is from Kaveri Pohlman with BTIG. Please proceed with your question.
Speaker Change #108: Thank you. Our next question is from Caveri Polman with BTG. Please proceed with your question.
Kaveri Pohlman: Great. Good evening.
Kaveri Pohlman: Hey, good evening, thanks, Congrats on the progress and thanks for taking my question.
Kaveri Pohlman: Congratulations on the progress and thanks for taking my question. For Rho2ADC in head and neck, can you tell us what feedback you have received from physicians on this data? And were there any patients who had seen any other Vidodin ADC as a prior line of therapy, whether it's PADSEV or KivDAC? Also, how are you thinking about the competitive landscape in general?
Kaveri Pohlman: Really two ADC in head and neck can you tell us what feedback you've received from physicians on this data and where do you get any patients who had seen any other window at an ADC as prior line of therapy, whether it's <unk> or Kim Jack also how you're thinking about the competitive landscape in general.
Eric L. Sievers: Thanks, Kaveri. It's Eric answering.
Eric Smith: Thanks, Caveri, it's Eric answering so first your question about the feedback we've gotten from physicians I'll just give you some anecdotes.
Speaker Change #110: We received a call from the P. I at U S C, indicating how pleased he was to report a complete response.
Eric L. Sievers: So first, your question about the feedback we've gotten from physicians. I'll just give you some anecdotes. We received a call from the PI at USC indicating how pleased he was to report a complete response, and that's now confirmed and enabling the patient to go back to work. And that's a patient that we review in our corporate deck. We were also pleased to hear from Memorial Sloan Kettering, where two of the investigators spoke about several patients on treatment, particularly emphasizing tolerability and the rapidity of response.
Eric Smith: And that's now confirmed and enabling the patient to go back to work.
Eric Smith: And that's a patient that we review in our corporate deck.
Speaker Change #117: We were also pleased to hear from Memorial Sloan Kettering, where two of the investigators spoke about several patients on treatment, particularly emphasizing the tolerability and the rapidity of response.
Eric L. Sievers: They felt that it really was serving an unmet need in this second, third, and fourth line head and neck cancer, which is exceptionally challenging, and so many patients have clinical progression as they're getting these therapies. And then you asked the question about whether patients had prior treatment with one of the other ADCs or statin-based ADCs. When I looked through the prior treatments, all patients had received a PD-1 blocking agent, and many received either a platinum and or a taxing regimen. I didn't see any anecdotes of people that had received prior ADCs, but it's certainly an interesting question with regard to the studies that are ongoing.
Kaveri Pohlman: They felt that it it really was serving them.
Kaveri Pohlman: The unmet need and that's second third and fourth line head and neck cancer, which is exceptionally challenging and so many patients having clinical progression as theyre getting these therapies and then you asked the question about did prior.
Speaker Change #113: Treatment with one or the other or a statin based adcs when I look through the prior treatments all patients had received a PD one blocking agents many received either a platinum or <unk> a taxane.
Kaveri Pohlman: Regimen.
Speaker Change #115: I didn't see any anecdotes of people that had received prior a D. CS.
Speaker Change #116: But it but it's certainly an interesting question with regard to the studies that are ongoing.
Sheri Lydick: Yeah, and Kaveri, this is Sheri. I can take the question on the competitive landscape. You know, obviously, within the existing competitive landscape, there remains a profound unmet need in patients who fail frontline options, as you know, in second line. Cetuximab is often used within ORR 13%. So we think, you know, within the existing therapeutic landscape, that there remains an unmet need. And even if you look at the future competitive landscape, we have a different mechanism of action, you know, than those that are in development.
Speaker Change #116: Yeah.
Jerry: This is Jerry I guess if.
Jerry: I can take the question on the competitive landscape.
Jerry: Now obviously with the existing competitive landscape. There. The main is a profound unmet need and patients who failed frontline options as you know in second line.
Speaker Change #119: She took some ads is.
Jerry: You are within or 13%. So we think you know within the existing therapeutic landscape. There remains an unmet need and even if you look at the future competitive landscape. Yeah. We have we have a different mechanism mechanism of action.
Jerry: You know there's those that are that are in development and we think that the profile that's emerging in the very heavily pretreated patient population.
Sheri Lydick: And we think that the profile that's emerging in this very heavily pretreated patient population really provides the opportunity for us to benefit patients in the second line setting within the existing as well as the future competitive landscape.
Speaker Change #118: Oh really.
Speaker Change #120: It really provides the opportunity for us.
Speaker Change #120: To benefit patients in the second line setting within the existing as well as the future competitive landscape.
Jay M. Short: Got it. That's very helpful. And maybe a question on the dosing regimen. I guess this is for both Actyl and Rho2ADC. You've tested different regimens from your initial schedule of Q2W2 to Q3W. Is this just for Project Optimist? Can you tell us what has been learned regarding the profile of the drug from these studies, whether you saw any significant PKPD differences with these regimens, and how you are thinking about the dosing schedule going forward?
Speaker Change #127: Got it that's very helpful and maybe a question on the dosing regimen I guess this is for both oxo lingual two ADC you've tested different regimens from your initial schedule of Q2 W. Two to Q3 W. Is this Jeff our project Optimus can you tell us what has been.
Speaker Change #120: Regarding the profile of the drug from these studies, whether you saw any significant PK P. D differences with these regimen and how you are thinking about dosing schedule going forward.
Jay M. Short: I'll just start off by saying, I'll let Eric finish this, but I just want to say I'll remind us all that we did use 2Q3W in phase one. So it's not that new. It's certainly one we've looked at. But with respect to 2Q3W and certain characteristics, I'll let Eric add to this.
Speaker Change #121: I'll just start off by saying all of the Erik finish this but I just want to say I'll remind us all that we did use the two Q3 W. In phase one so it's not.
Speaker Change #125: That news certainly when we've looked at about with respect to Q3 W. A certain characteristics and I'll, let Eric add to this.
Eric L. Sievers: Sure. Thanks, Jay.
Jay: Thanks, Jay So I'll emphasize that bolstered the regimens I think are exceptionally well tolerated.
Eric L. Sievers: So, I'll emphasize that both of the regimens, I think, are exceptionally well-tolerated. I'll refer everyone to slide 35 of our corporate deck, where we've summarized the every-other-week dosing, the 223W, which is days one and eight of a three-week cycle, and then for melanoma as well. And here, we're having very few instances of related AEs leading to treatment discontinuation. And so, tolerability is excellent with both regimens. We are seeing in the head and neck data, in particular, I think you can see from the spider plot on slide 28, just a sense that we get more rapid disease control in the red, which is the more intensive regimen than the blue.
Speaker Change #122: I'll refer everyone to slide 35 of our corporate deck, where we've summarized.
Eric Smith: The every other week dosing that two to three W. Which is days one and eight of a three week cycle and then for melanoma as well and in here, we're having very few instances of related aes, leading to treatment discontinuation and so tolerability was excellent with both regimens we are seeing.
Speaker Change #122: In the head and neck data in particular, I think you can see from the Spider plot on on slide 28.
Melanoma: Our sense that we get more rapid disease control in the Red which is the more intensive regimen then the blue.
Melanoma: And it is interesting with the blue patient so they did have longer exposure.
Eric L. Sievers: And it is interesting with the blue patients; they did have longer exposure because we did those patients first. And there are quite a few patients, there are two instances of patients that have been on many, many weeks of therapy, one passing 35 weeks and one passing 45 weeks on study. So, I think both regimens are well-tolerated, and the PKPD, no surprises there. So, it's looking good.
Speaker Change #124: Because we did that those patients first and there there are quite a few patients there. The two instances of patients that are at many many weeks of therapy, one passing 35 weeks in one passing 45 weeks on study so.
Speaker Change #124: I think I think both regimens well tolerated and the PK P. D. No surprises there so I'm looking to it.
Kaveri Pohlman: That's helpful. Thanks for taking my questions.
Speaker Change #126: That's helpful. Thanks for taking my questions.
Speaker Change #126: Yeah.
Operator: Thank you. Our next question is from Arthur He with HC Wainwright. Please proceed with your question.
Speaker Change #126: Thank you. Our next question is from Arthur He with H C. Wainwright. Please proceed with your question.
Arthur He: Hey Jay and team, good afternoon. Thanks for taking my question. And congrats on the data in the head and neck. I just had a couple of questions for the head and neck data. First, as I recall, you mentioned you wanted to go for a first line for these R02-ADCs. First, I just want to get your priority here for the future, or still depending on the discussion with the FDA in the second half.
Arthur He: Hey, Jay and team and good afternoon. Thanks for taking my question and congrats on the data in head and neck.
Arthur He: I just had a couple of questions for the <unk>.
Speaker Change #128: Next data.
Speaker Change #128: So.
Speaker Change #128: First.
Speaker Change #128: I recall, you mentioned you want to go for a first line.
Speaker Change #129: But these are two ADC.
Speaker Change #129:
Speaker Change #128: First I just wanted to get gauging your priority here for the future or is it still depending on the discussion with the FDA in the second half.
Speaker Change #131: Thank you Arthur I appreciate that we haven't.
Arthur He: Thank you, Arthur. I appreciate it.
Speaker Change #133: Made a formal decision about whether we're going to target first or second or balls, yet our vision is that we'd like to go to the agency and discuss trial designs for both for.
Eric L. Sievers: We haven't made a formal decision about whether we're going to target first or second or both yet. Our vision is that we'd like to go to the agency and discuss trial designs for both. For the first line, I think that orostatin-based ADCs pair remarkably well with PD-1 blockade, and so I think it'd be an excellent combination with the PD-1 antibody in first line patients that receive just the PD-1 antibody alone.
Speaker Change #131: For the first line I think that the or statin based Adcs Park.
Speaker Change #131: There are remarkably well with PD, one blockade and so I think it would be a really an excellent combination with a PD one antibody in the first line patients that received just.
Speaker Change #132: The PD one antibody alone.
Eric L. Sievers: And then we could, of course, do a phase one evaluation in combination with platinum PD-1 to further enable that. Moving to second grade and beyond. Second, and beyond that line, there's an enormous unmet need, and we see a relatively straightforward trial design where we would compare either cituximab monotherapy or potentially a limited number of chemotherapy or cituximab choices for the investigator with a PFS endpoint that might possibly enable an early review of the trial data and accelerated approval, and then with an OS endpoint that would confirm that in the same trial. So these are the possibilities that we are looking forward to exploring with the agency.
Speaker Change #132: And then we could of course do a phase one evaluation in combination with platinum and PD one to further enable that moving to second and beyond.
Speaker Change #134: And beyond line, there's an enormous unmet need and we see a relatively straightforward trial design, where we would compare either against the tux them that monotherapy or potentially a limited number of chemotherapy or cetuximab choices for the investigator with a PFS endpoint.
Speaker Change #134: That might possibly enable an early review of the trial data and accelerated approval and then with an OS endpoint that would confirm in the same trial. So these are the possibilities that we are looking forward to exploring with the agency.
Eric L. Sievers: Thanks, Eric. Very helpful. And regarding the data, it seems like the 2Q3W has a better response compared to the Q2W. And I'm just curious, is there any correlation between the HPV expression marker in these patients and the response rate with the HPV expression there?
Speaker Change #137: Thanks, Eric.
Speaker Change #139: And regarding the data it seems like the <unk>.
Speaker Change #135: Q3 debut has.
Speaker Change #138: A better response compared to the Q2 W and.
Speaker Change #136: Just curious hum.
Speaker Change #136: Looking into the the HPV expression.
Speaker Change #141: Mark or in these patients is there any correlation in the.
Speaker Change #136: Regarding the response rates are.
Speaker Change #140: We see HPV HPV expression there.
Eric L. Sievers: Yeah, it's a great question, Arthur. But we have not seen a correlation with HPV expression. It's something that we're going to continue to look at very closely. Those patients receive therapy that's a little bit different. There's some recent data suggesting they can de-escalate aggressive early therapy, and so we've been guided by our investigators to think of them as a little bit different than the HPV negative population. But right now, I'm not seeing any obvious correlations. And I'll just add that we're also not seeing obvious correlations with the ROR2 expression, because that's often a question that people ask us. And so we're not needing a companion diagnostic at this time.
Speaker Change #143: Yeah, It's a great question Arthur.
Speaker Change #142: We have not seen a correlation with HPV expression, it's something that we're going to continue to look at very closely those patients receive therapy, that's a little bit different there are some recent data, suggesting they can deescalate the aggressive early therapy and so we've been guided by our investigators to think of.
Speaker Change #142: Of them is a little bit different than the H P V knee and negative population, but right now I'm not seeing any obvious correlations and I'll just add that we're also not seeing obvious correlations with the R. O R. Two expression.
Speaker Change #140: Because that's often a question that people ask us and so we're not meeting our companion diagnostic at this time.
Arthur He: If I may, for the CTLA-4 program, for the upcoming data for the monotherapy this quarter, could you give us a little bit more color on the cancer type for those 20 patients as well as, as of now, what's the medium cycle number of patients receiving the drug?
Speaker Change #140: Gotcha.
Speaker Change #155: If I may for the securities.
Speaker Change #147: Kelly for a program for.
Speaker Change #146: For the upcoming data from the monotherapy in this quarter.
Speaker Change #144: Could you give us a little bit more color on the.
Kelly <unk>: Cancer types for those Twain, a patient as well as as I'm now, what's the medium cycle number as patient received the drug.
Eric L. Sievers: Okay, so moving to conditionally binding CTLA-4, and you're asking about monotherapy, we open the doors very wide to melanomas and relapse-refractory carcinomas. So I would anticipate a very broad number of different ones, you know, single patients with different unusual cancer diagnoses that sometimes weren't eligible for other clinical trials that were participating in the monotherapy experience.
Speaker Change #149: Okay, So moving to the conditionally binding see till a four and you're asking about the monotherapy. We opened the doors very wide two melanomas and relapsed refractory carcinomas, So I I would.
Speaker Change #145: Anticipate a very broad.
Speaker Change #140: A number of different one single patients with different unusual.
Speaker Change #140: Cancer diagnoses that sometimes weren't eligible for other clinical trials that we're participating in the monotherapy experience.
Eric L. Sievers: Our overall goal with monotherapy was to clearly characterize the safety profile at both 350 and 700 milligrams. And I'm also happy to say that today, we treated the third patient at the one gram dosing level. So we've now infused all three of the individuals at the very high dose level of one gram, which is 14.2 milligrams per kilogram, based on a 70 kilo adult. So we're looking forward to the ASCO presentation on June 1st, and then a subsequent presentation to describe the outcome of these monotherapy patients that you've just asked about.
Speaker Change #140: Our overall goal with the monotherapy was too clearly characterize the safety profile at both 350 700 milligrams and I'm also happy to say that today, we treated the third patient at the one gram dosing level. So we've now infused all three of the.
Speaker Change #140: Digital is at the very high dose level of one Gram, which is $14 two milligrams per kilogram based on a 70 kilo adult.
Speaker Change #152: So we're looking forward to fiasco presentation on June 1st and then a subsequent presentation to describe the outcome of these monotherapy patients that you've just asked about.
Arthur He: Great. Thanks, Eric. Thanks for taking my question.
Speaker Change #156: Great. Thanks, Eric Thanks for taking my question.
Operator: Thank you. Our next question is from Tony Butler on behalf of EF Hutton. Please proceed with your question.
Speaker Change #150: Thank you. Our next question is from totally Tony Butler with <unk>. Please proceed with your question.
Tony Butler: Yes, thanks very much. I'd like to go back to the previous question, if I may, and Part A: again, this is with CTLA-4. Will there be, or do you anticipate, and I assume you will, that the combination with Pembro, at one gram, will have been sufficiently, have a sufficient duration before you make a decision about moving forward in the BRAF mutated melanoma study? That's part one. And part two of that is apparently from the comparator arm; you're making some judgments that there may be other types of agents that could be utilized other than PEMBRO. And I'm just curious, does this end up simply being the physician's choice in frontline? And then I have one more follow-up question, if I may.
Speaker Change #150: Yes, thanks very much.
Speaker Change #148: Like to go back to the previous question if I may.
Speaker Change #157: And part of it you can this is lets see tell a four.
Speaker Change #158: Will there be or do you anticipate I mean, I assume you will that the.
Speaker Change #153: Nation with Pembroke at one Gram will have been sufficiently hum.
Speaker Change #153: We have sufficient duration.
Speaker Change #153: You make a decision about moving forward in the <unk>.
Speaker Change #153: <unk> mutated melanoma study, that's part one and part two of that is.
Speaker Change #148: Apparently from the comparator arm youre, making some judgments that there may be other.
Speaker Change #154: Uh huh.
Speaker Change #161: Types of agents that could be utilized other than Pembroke and I'm. Just curious does this end up simply being physician's choice in frontline and then I have one more follow up if I may thank you.
Eric L. Sievers: So why don't I take these in sequence? So the very first question you asked is, will we have sufficient follow-up? And we believe we will.
Speaker Change #160: So why don't I take take these in sequence. So the very first question. You asked is will we have sufficient follow up and we believe we will so I want to affirm that we are currently dosing patients with newly diagnosed melanoma met.
Eric L. Sievers: So I want to affirm that we are currently dosing patients with newly diagnosed melanoma, metastatic or unresectable melanoma, and presently, without regard to BRAF mutation, yet to gain additional experience at this dose level. So these are first-line patients, I just want to emphasize that, because that is then going to lead into the proposed pivotal trial. Your second question is a really interesting one, and I think that agency feedback will be necessary here.
Speaker Change #154: Static or unresectable melanoma, and presently without regard to BRAF mutation.
Speaker Change #154: Two to get to gain additional experience at this dose level.
Speaker Change #154: So these are first line patients. So I just wanted to emphasize that.
Speaker Change #154: Because that is then going to then lead into the proposed pivotal trial here.
Speaker Change #154: Your second question, it's a really interesting one and I think that agent.
Speaker Change #154: Agency feedback will be necessary here I want to remind everyone that there are four strategies that could be employed for newly diagnosed metastatic.
Eric L. Sievers: I want to remind everyone that there are four strategies that could be employed for newly diagnosed metastatic or unresectable melanoma, and they include nivolumab, pembrolizumab, OptuLag, or the combination of nivolumab plus ipilimumab. And so our vision presently is that we'd like to run a blinded, randomized study against pe And it's notable that several other sponsors are using Pembrolizumab monotherapy as the comparator arm in their frontline melanoma trials.
Speaker Change #154: Or unresectable melanoma and they include Nivola, Matt Henn Burleson, Matt both of those as monotherapy.
Speaker Change #154: Do lag.
Speaker Change #154: Or the combination of <unk> plus it would be linear math.
Speaker Change #154: So our vision presently is that we'd like to run a blinded randomized study against pemble isn't bad because it represents a currently labeled the opportunity and it's notable that several other sponsors are using <unk> monotherapy as the comparator arm in their frontline melanoma trials.
Eric L. Sievers: Eric, thank you for the follow-up or the commentary. My follow-up question is on the Nectin 4 ADC with the carbohydrate linker. Just mechanistically, does the carbohydrate linker limit the amount of the payload that you can actually add to the antibody? And if you say no, that's fine.
Eric Smith: Eric Thank you for the follow up.
Speaker Change #163: The the commentary my follow up question is on the back and forth.
Speaker Change #154: D C.
Speaker Change #162: With the carbohydrate linker.
Speaker Change #159: Just mechanistically.
Speaker Change #154: The carbohydrate link or limit the number of.
Speaker Change #154: The payload, which you can actually add to.
Speaker Change #154: To the antibody and if you say no that's fine.
Tony Butler: But the question is, what is the DAR today? Is that the most optimal payload or the Nectin 4 ADC? Thanks very much.
Speaker Change #166: But the question is what is the door today is that the most optimal payload or the Mexican for PBC. Thanks very much.
Jay M. Short: I'll take that one. Basically, the actual design of the carbohydrate linker system allows us to go above the DAR4. So actually, the current Nectin 4 ADC is DAR6, and we've seen a very good safety profile. We think it's going to add to the safety profile because it's going to help us to reduce off-target tox. In addition, it's also a CAB, so it further reduces on-target tox.
Speaker Change #165: I'll take that one and Tony I'm basically the actual design of the carbohydrate linker system allows us to increase above the Dar for so actually that are current.
Speaker Change #164: Mexico for ADC as Dar sex.
Speaker Change #167: And we are and we've seen a very good safety profile, we think it's going to add to the safety profile, because if it's going to help us to reduce off target talks. In addition, it's also a cab. So further reduces on target talk so we're really bringing these two pieces together.
Jay M. Short: So we're really bringing these two pieces together and in a very specific way because, you know, Nekton-4, the marketed compound, is known to have various toxicities, and one of those is significant as a rash. And so we, at least from the animal data and from modeling, suggest that we have a therapeutic index of Additional Targets Not Traditionally Associated with Nectin-4 Activity, and one of those is pancre And we do know that this observation is linked in part to our carbohydrate linker and the CAB and protein linker working together.
Speaker Change #154: In a very specific way because you know in Mexico for the Mark of the compound is known to have various toxicities and one of the one of those is significant there's a rash and so we at least from the animal data and for modeling suggests that we have a therapeutic index.
Speaker Change #154: Should allow us to be able to reduce if not totally eliminate the rash and we'll just have to see the data further we're kind of we're excited about this drug because we have also the other side we've been enable it had the ability to enable AR.
Speaker Change #154: Additional targets not traditionally associated with Nexen for activity in one of those is pancreatic cancer and we do know that this observation is linked to in part to our carbohydrate linker and the cab and carbohydrate Linky linker working together, however, it and saying all of this I want to emphasize.
Jay M. Short: However, in saying all of this, I want to emphasize that there's no way I think of saying that the carbohydrate linker is better than what we've seen with the peptide linker in Axel and ROR2 because we had a very specific toxicity to resolve anectin-4. We are seeing very safe profiles without those kind of toxicities with our Axel and ROR2 drugs. So I think in a way we came into this program with a very specific purpose to address a very clearly defined toxicity.
Speaker Change #154: Is that there's no way I'd say.
Speaker Change #154: Is.
Speaker Change #154: Saying that the carbohydrate Lakers better than what we've seen with the peptide linker in actual award to because we don't we had a very specific toxicity to resolve a negative four we are seeing varies a safe profile without those kinds of toxicities with our actual Aurora two drugs. So I think in a way we came in to this program.
Speaker Change #154: A very specific purpose to address a very clearly defined toxicity and so in combination you have a chance here that go in to Ah indication with a very low bar.
Jay M. Short: And so, in combination, you have a chance here to go into an indication with a very low bar for safety that could potentially allow this drug to go quite wide. And I'll just add that I think one nice thing about it is that you should get these results very quickly because there's a known level of dosing. And so with phase one, you should learn both your safety and your efficacy enough to really validate this compound. So an exciting asset.
Speaker Change #154: With safety that could potentially allow this drug to go quite wide and I'll just add I think one nice thing about it is that you should get these results very quickly because there's no level of dosing and so with phase one you should learn both your safety and efficacy adequate to really validate those compounds. So.
Speaker Change #154: An exciting asset.
Speaker Change #154: Yeah.
Tony Butler: Jay, it's fantastic. Thanks very much.
Speaker Change #168: That's fantastic thanks very much.
Operator: Thank you. There are no further questions at this time. I'd like to hand the floor back over to Jay Short, CEO, for closing comments.
Speaker Change #170: Thank you there are no further questions at this time I'd like to hand, the floor back over to Jay Schwartz CEO for closing comments.
Jay M. Short: Thank you everyone for your attendance today and your continued interest in Bioatla. We're obviously very encouraged by our data and very hopeful, and a lot of drugs that I think are on the precipice of being able to bring to market, so hopefully, it continues, and thank you for your attention.
Jay M. Short: And thank you everyone for your attendance today and continued interest in <unk>. We're obviously very encouraged by our data and very hopeful.
Operator: This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.
Jay M. Short: A lot of drugs that I think are on the precipice of being able to bring to market. So hopefully that continues and thank you for your attention.
Speaker Change #169: This concludes today's conference you may disconnect your lines at this time. Thank you for your participation.