IDEAYA Biosciences Inc

Previous wording

Our clinical pipeline includes four potential first-in-class clinical-stage product candidates – darovasertib (PKC), IDE397 (MAT2A), IDE161 (PARG) and GSK101 (Pol Theta Helicase). We own or control all commercial rights of the three most-advanced of these product candidates: darovasertib, IDE397, and IDE161. We are also advancing our Werner Helicase program for which a development candidate has been selected in collaboration with GlaxoSmithKline, or GSK and, subject to investigational new drug-, or IND-, enabling studies, are targeting an IND in 2024. In July 2024, we entered into an Option and License Agreement with Biocytogen Pharmaceuticals (Beijing) Co., Ltd., or Biocytogen, pursuant to which Biocytogen granted to us an option for an exclusive worldwide license to develop and commercialize products in connection with a potential first-in-class B7H3/PTK7 topo-I-payload bispecific antibody drug conjugate program. We also have multiple earlier-stage preclinical programs. We have established selective, value-accretive collaborations with leading pharmaceutical companies to support our clinical development activities.

Current wording

Our clinical pipeline includes five potential first-in-class clinical-stage product candidates – darovasertib (PKC), IDE397 (MAT2A), IDE161 (PARG), IDE705 / GSK101 (Pol Theta Helicase), and IDE275 / GSK959 (Werner Helicase). We own or control all commercial rights of the three most-advanced of these product candidates: darovasertib, IDE397, and IDE161. In July 2024, we entered into an Option and License Agreement with Biocytogen Pharmaceuticals (Beijing) Co., Ltd., or Biocytogen, pursuant to which Biocytogen granted to us an option for an exclusive worldwide license to develop and commercialize products in connection with a potential first-in-class B7H3/PTK7 topo-I-payload bispecific antibody drug conjugate program for which we are targeting a development candidate in the fourth quarter of 2024. We also have multiple earlier-stage preclinical programs. We are targeting development candidate nominations in the fourth quarter of 2024 for multiple new targets, or NTs, including a development candidate to treat MTAP-deletion solid tumors to enable a potential wholly-owned clinical combination with IDE397, and we are separately targeting a development candidate for a potential first-in-class program in the KAT6 pathway. We have established selective, value-accretive collaborations with leading pharmaceutical companies to support our clinical development activities.

Previous wording

We have achieved triple-digit patient enrollment and have opened multiple clinical sites, including international sites, in our potential registration-enabling Phase 2/3 clinical trial, designated as IDE196-002. The purpose of the clinical trial is to evaluate darovasertib in combination with crizotinib, Pfizer’s investigational cMET inhibitor, in patients having metastatic uveal melanoma, or MUM, with human leukocyte antigen-, or HLA-A*02:01 negative, or HLA-A2(-), serotype, as part of a second Clinical Trial Collaboration and Supply Agreement, or Second Pfizer agreement, with Pfizer.

Current wording

We have enrolled over 150 patients as of October 31, 2024, and have opened multiple clinical sites, including international sites, in our potential registration-enabling Phase 2/3 clinical trial, designated as IDE196-002. The purpose of the clinical trial is to evaluate darovasertib in combination with crizotinib, Pfizer’s investigational cMET inhibitor, in patients having metastatic uveal melanoma, or MUM, with human leukocyte antigen-, or HLA-A*02:01 negative, or HLA-A2(-), serotype, as part of a second Clinical Trial Collaboration and Supply Agreement, or Second Pfizer agreement, with Pfizer.

Previous wording

We are planning to enroll additional HLA-A*02:01 positive, or HLA-A2(+), patients as an independent clinical strategy to address HLA-A2(+) MUM patients, in our ongoing Phase 2 clinical trial, designated as IDE196-001. We are further evaluating darovasertib in combination with crizotinib in the Phase 2 expansion arm of IDE196-001 in patients with GNAQ/11 melanomas, including metastatic cutaneous melanoma.

Current wording

We are planning to enroll additional HLA-A*02:01 positive, or HLA-A2(+), patients as an independent clinical strategy to address HLA-A2(+) MUM patients, in our ongoing Phase 2 clinical trial, designated as IDE196-001.

Previous wording

We separately initiated and have achieved double-digit patient enrollment in our Phase 2 clinical trial, designated as IDE196-009, evaluating darovasertib as single-agent neoadjuvant and adjuvant therapy in patients having primary uveal melanoma, or UM, with ongoing enrollment and multiple clinical sites open. We have scheduled a Type C meeting with the U.S. Food and Drug Administration, or FDA, to discuss a potential registrational trial in the neoadjuvant UM setting in the third quarter of 2024 and are targeting a clinical efficacy update in over 30 patients in the second half of 2024.

Current wording

We have enrolled over 75 patients as of October 31, 2024, in our Phase 2 clinical trial, designated as IDE196-009, evaluating darovasertib as single-agent neoadjuvant and adjuvant therapy in patients having primary uveal melanoma, or UM, with ongoing enrollment and multiple clinical sites open. In September 2024, we announced interim clinical data from the ongoing Phase 2 company-sponsored trial and provided a regulatory update on a registrational trial based on a Type C meeting held with the U.S. Food and Drug Administration, or FDA.

Previous wording

The potentially addressable patient population for MUM is estimated to include an annual incidence of approximately 4,500 patients across the United States, or U.S., and Europe, with an estimated total prevalence of approximately 14,000 patients in the U.S. and Europe. (Neo)Adjuvant UM represents a significant expansion opportunity for darovasertib – with a potential annual incidence of approximately 8,700 patients aggregate in U.S. and Europe and with an estimated total prevalence of approximately 100,000 patients in the U.S. and Europe.

Current wording

The potentially addressable patient population for MUM is estimated to include an annual incidence of approximately 4,500 patients across the United States, or U.S., and Europe. (Neo)Adjuvant UM represents a significant expansion opportunity for darovasertib – with a potential annual incidence of approximately 12,000 patients aggregate in North America, Europe and Australia.

Previous wording

In parallel, we are continuing to evaluate darovasertib in our ongoing Phase 2 clinical trial, designated as IDE196-001, as a combination therapy with crizotinib in MUM patients. We are the sponsor of this Phase 2 clinical trial and are collaborating with Pfizer on this Phase 2 clinical trial pursuant to the Pfizer Agreement.

Current wording

In parallel, we are continuing to evaluate darovasertib in our ongoing Phase 2 clinical trial, designated as IDE196-001, as a combination therapy with crizotinib in HLA-A2(+) MUM patients. We are the sponsor of this Phase 2 clinical trial and are collaborating with Pfizer on this Phase 2 clinical trial pursuant to the Pfizer Agreement.

Previous wording

We are planning to enroll additional HLA-A*02:01 positive, or HLA-A2(+), patients as an independent clinical strategy to address HLA-A2(+) MUM patients, in our ongoing Phase 2 clinical trial, designated as IDE196-001. This strategy demonstrates our commitment to fully address the high unmet medical need in MUM. Such clinical trial data from darovasertib and crizotinib combination treatment in HLA-A2(+) MUM could support publication and potential inclusion in NCCN Clinical Practice Guidelines in Oncology.

Current wording

We are planning to enroll additional HLA-A2(+) MUM patients as an independent clinical strategy to address HLA-A2(+) MUM patients, in our ongoing Phase 2 clinical trial, designated as IDE196-001. This strategy demonstrates our commitment to fully address the high unmet medical need in MUM. Such clinical trial data from darovasertib and crizotinib combination treatment in HLA-A2(+) MUM could support publication and potential inclusion in NCCN Clinical Practice Guidelines in Oncology.

Previous wording

Darovasertib - Neoadjuvant and Adjuvant Therapy in Uveal Melanoma (UM)

Current wording

Darovasertib – Phase 2 Trials in Neoadjuvant and Adjuvant Therapy in Uveal Melanoma (UM)

Previous wording

We have initiated and achieved double-digit patient enrollment in our company-sponsored Phase 2 clinical trial designated as IDE196-009, with ongoing enrollment and multiple clinical sites open. The purpose of the clinical trial is to evaluate single-agent darovasertib as neoadjuvant treatment of primary UM prior to primary interventional treatment of enucleation or radiation therapy and also as adjuvant therapy following the primary treatment.

Current wording

We have initiated and achieved double-digit patient enrollment in our company-sponsored Phase 2 clinical trial designated as IDE196-009, with ongoing enrollment and multiple clinical sites open. The purpose of the clinical trial is to evaluate single-agent darovasertib as neoadjuvant treatment of primary UM prior to primary interventional treatment of enucleation or radiation therapy and also as adjuvant therapy following the primary treatment. An amendment to the study protocol was submitted to the FDA in July 2024 to enable dosing of darovasertib therapy up to 12 months.

Previous wording

We are enrolling patients into a Phase 1/2 clinical trial designated as IDE397-001 to evaluate IDE397 for patients having certain tumors with MTAP gene deletion. We are proceeding with enrollment of MTAP-deletion patients into a monotherapy Phase 1/2 expansion cohort with an initial focus on high priority solid tumor types, including squamous non-small cell lung cancer, or NSCLC, and urothelial cancers. We have selected a move-forward Phase 1/2 expansion dose for IDE397 monotherapy in MTAP-deletion squamous NSCLC and urothelial cancer, based on adverse event profile and preliminary clinical efficacy observed, including multiple partial responses by RECIST 1.1. The estimated U.S. MTAP-deletion annual incidence in squamous NSCLC and urothelial cancer is approximately 48,000 patients.

Current wording

We are enrolling patients into a Phase 1/2 clinical trial designated as IDE397-001 to evaluate IDE397 for patients having certain tumors with MTAP gene deletion. We are proceeding with enrollment of MTAP-deletion patients into a monotherapy Phase 1/2 expansion cohort with an initial focus on high priority solid tumor types, including urothelial cancer, or UC, and non-small cell lung cancer, or NSCLC. We have selected a move-forward Phase 1/2 expansion dose for IDE397 monotherapy in MTAP-deletion UC and NSCLC, based on adverse event profile and preliminary clinical efficacy observed, including multiple partial responses by RECIST 1.1. The estimated U.S. MTAP-deletion annual incidence in UC and NSCLC is approximately 48,000 patients.

Previous wording

In July 2024, we announced clinical data for the IDE397 Phase 1/2 monotherapy expansion dose demonstrating preliminary clinical efficacy in heavily pre-treated MTAP-deletion urothelial cancer and squamous NSCLC patients. The patients evaluated had a median of two prior lines of therapy, ranging from one to nine prior lines of treatment. The reported Phase 1/2 clinical data were based on 18 evaluable MTAP-deletion patients, including seven urothelial cancer patients, four adenocarcinoma squamous NSCLC patients, and seven squamous NSCLC patients at the expansion dose of 30 mg once-a-day, or QD, of IDE397. In the interim update for 18 evaluable patients, with a data analysis cutoff date of June 21, 2024, we reported an overall response rate of approximately 39% (one complete response and six partial responses by RECIST 1.1 evaluation), which includes two unconfirmed partial responses (one urothelial cancer patient that had a 100% tumor reduction in the target lesion at the last CT-scan assessment that has now been confirmed and one adenocarcinoma squamous NSCLC patient that is awaiting confirmation as of July 31, 2024). We also observed a disease control rate of 94%, including one complete response, six partial responses and ten stable disease by RECIST 1.1 evaluation. In addition, we observed tumor shrinkage in 14 of the 18 evaluable patients. 11 of the evaluable patients are still on treatment and five of the seven responses by RECIST 1.1 evaluation remain in response. We also reported a ctDNA molecular response, or MR, rate of 81%, representing 13 of 16 reportable patients with 50% or greater ctDNA reduction (several quality control failures of patient samples precluded the other patients from MR analysis).

Current wording

June 21, 2024, we reported an overall response rate of approximately 39% (one complete response and six partial responses by RECIST 1.1 evaluation), which included two unconfirmed partial responses (one UC patient that had a 100% tumor reduction in the target lesion at the last CT-scan assessment and one adenocarcinoma squamous NSCLC patient which were both confirmed in the Company's October 2024 update). We also observed a disease control rate of 94%, including one complete response, six partial responses and ten stable disease by RECIST 1.1 evaluation. In addition, we observed tumor shrinkage in 14 of the 18 evaluable patients. 11 of the evaluable patients are still on treatment and five of the seven responses by RECIST 1.1 evaluation remain in response. We also reported a ctDNA molecular response, or MR, rate of 81%, representing 13 of 16 reportable patients with 50% or greater ctDNA reduction (several quality control failures of patient samples precluded the other patients from MR analysis).

Previous wording

In August 2023, Amgen initiated and dosed a first patient in the IDE397 /AMG 193 combination study, following FDA authorization to proceed with the clinical trial. This Phase 1/2 clinical trial (NCT: 05975073) will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with AMG 193, with an initial focus for expansion in NSCLC patients and an estimated enrollment of approximately 180 patients. Enrollment is ongoing in the dose escalation portion of this Phase 1/2 clinical trial. We are targeting the development of a joint publication strategy in 2024. Separately, in consultation with Amgen, we have now financially budgeted to support our obligations for target IDE397 / AMG 193 clinical combination expansion in NSCLC.

Current wording

In August 2023, Amgen initiated and dosed a first patient in the IDE397 /AMG 193 combination study, following FDA authorization to proceed with the clinical trial. This Phase 1/2 clinical trial (NCT: 05975073) will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with AMG 193, with an initial focus for expansion in NSCLC patients and an estimated enrollment of approximately 180 patients. Enrollment is ongoing in the dose escalation portion of this Phase 1/2 clinical trial [and are targeting an expansion in MTAP-deletion NSCLC in late 2024 to early 2025]. We presented a preclinical poster presentation on the antitumor activity by combinatorial inhibition of MAT2A and PRMT5 in MTAP-deleted tumors at ENA 2024.

Previous wording

We are separately collaborating with Gilead to clinically evaluate IDE397 in combination with sacituzumab-govitecan-hziy, or Trodelvy, Gilead’s Trop-2 directed anti-body conjugate, or ADC, in patients having MTAP- deletion urothelial cancer, in our Phase 1 clinical trial pursuant to a Clinical Study Collaboration and Supply Agreement, or Gilead CSCSA, with Gilead Sciences, Inc., or Gilead. A first patient was dosed for the Phase 1 trial in June 2024 and enrollment is ongoing.

Current wording

We are separately collaborating with Gilead Sciences, Inc., or Gilead, to clinically evaluate IDE397 and Trodelvy (sacituzumab-govitecan-hziy), Gilead’s Trop-2 directed ADC combination, in patients having MTAP-deletion UC, in our Phase 1 clinical trial pursuant to a Clinical Study Collaboration and Supply Agreement, or Gilead CSCSA, with Gilead. A first patient was dosed for the Phase 1 trial in June 2024.

Previous wording

We are progressing with enrollment of patients having tumors with HRD into the Phase 1 expansion portion of the Phase 1/2 clinical trial in selected priority tumors. In parallel, we are also continuing with Phase 1 dose optimization to confirm a move-forward expansion dose for the planned Phase 2 portion of the clinical trial. We are targeting an initial Phase 2 monotherapy expansion in HRD solid tumors in the second half of 2024. We are also validating IDE161 combination opportunities preclinically and targeting identification of potential combination(s) in 2024.

Current wording

We are progressing with enrollment of patients having tumors with HRD into the Phase 1 expansion portion of the Phase 1/2 clinical trial in selected priority tumors. In parallel, we are also continuing with Phase 1 dose optimization to confirm a move-forward expansion dose for the planned Phase 2 portion of the clinical trial. We are targeting an initial Phase 2 monotherapy expansion in HRD solid tumors in the fourth quarter of 2024.

Previous wording

The expansion portion of the Phase 1 trial has a strategic focus in estrogen receptor positive, or ER+, human epidermal growth factor receptor 2 negative, or Her2(-), breast cancer with HRD, as well as other solid tumors with

Current wording

The expansion portion of the Phase 1 trial has a strategic focus in estrogen receptor positive, or ER+, human epidermal growth factor receptor 2 negative, or Her2(-), breast cancer with HRD, as well as other solid tumors with HRD, such as endometrial cancer, colorectal cancer and prostate cancer. The ER+, Her2-, HRD+ breast cancer focus represents approximately 10% to 14% of breast cancer patients.

Previous wording

In March 2024, we entered into the Merck CTCSA with MSD International Business GmbH, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. We are planning to evaluate IDE161 in a combination study with KEYTRUDA in patients with high microsatellite instability, or MSI, and microsatellite stable, or MSS, endometrial cancer. We are targeting a first-patient dosing for this study in the second half of 2024.

Current wording

In March 2024, we entered into the Merck CTCSA with Merck (known as MSD outside of the US and Canada). We are planning to evaluate the combination of IDE161 and KEYTRUDA® (pembrolizumab) in patients with high microsatellite instability, or MSI, and microsatellite stable, or MSS, endometrial cancer. We are targeting a first-patient dosing for this study in the fourth quarter of 2024.

Previous wording

GSK101 (IDE705) - Pol Theta Helicase Inhibitor in tumors with Homologous Recombination Deficiency

Current wording

IDE705 (GSK101) – Pol Theta Helicase Inhibitor in tumors with Homologous Recombination Deficiency

Previous wording

We discovered GSK101 (IDE705), our DNA Polymerase Theta, or Pol Theta, Helicase inhibitor clinical development candidate, and evaluated GSK101 in preclinical studies in collaboration with GSK. GSK101 targets the helicase domain of the Pol Theta protein for patients having solid tumors with BRCA or other mutations associated with HRD.

Current wording

We discovered IDE705 (GSK101), our DNA Polymerase Theta, or Pol Theta, Helicase inhibitor clinical development candidate, and evaluated IDE705(GSK101) in preclinical studies in collaboration with GSK. IDE705 (GSK101) targets the helicase domain of the Pol Theta protein for patients having solid tumors with BRCA or other mutations associated with HRD.

Previous wording

GSK is evaluating GSK101 in combination with niraparib, the GSK small molecule inhibitor of PARP for the treatment of patients having tumors with BRCA or other HR mutations, or HRD, in a GSK-sponsored Phase 1 clinical trial. GSK has dosed the first patient and enrollment is ongoing in the dose escalation portion of this study.

Current wording

GSK is evaluating IDE705 (GSK101) in combination with niraparib, the GSK small molecule inhibitor of PARP for the treatment of patients having tumors with BRCA or other HR mutations, or HRD, in a GSK-sponsored Phase 1 clinical trial. GSK has dosed the first patient and enrollment is ongoing in the dose escalation portion of this study.

Previous wording

GSK is leading clinical development of GSK101 pursuant to the Collaboration, Option and License Agreement with GSK, or GSK Collaboration Agreement. GSK is responsible for all research and development costs for the Pol Theta program.

Current wording

GSK is leading clinical development of IDE705 (GSK101) pursuant to the Collaboration, Option and License Agreement with GSK, or GSK Collaboration Agreement. GSK is responsible for all research and development costs for the Pol Theta program.

Previous wording

We have the potential to receive an additional $10.0 million milestone payment upon initiation of Phase 1 clinical dose expansion. In August 2023, we achieved and earned a $7.0 million milestone based on acceptance of the IND by the FDA, for which payment was received in October 2023. An earlier preclinical development $3.0 million milestone payment from GSK was achieved in August 2022 in connection with ongoing IND-enabling studies to support evaluation of GSK101.

Current wording

We have the potential to receive an additional $10.0 million milestone payment upon initiation of Phase 1 clinical dose expansion. In August 2023, we achieved and earned a $7.0 million milestone based on acceptance of the IND by the FDA, for which payment was received in October 2023. An earlier preclinical development $3.0 million milestone payment from GSK was achieved in August 2022 in connection with ongoing IND-enabling studies to support evaluation of IDE705 (GSK101).

Previous wording

We have the potential to earn further aggregate late-stage development and regulatory milestones of up to $465 million. Upon commercialization, we will be eligible to receive up to $475 million of commercial milestones, and tiered royalties on global net sales of GSK101 – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

Current wording

We have the potential to earn further aggregate late-stage development and regulatory milestones of up to $465.0 million. Upon commercialization, we will be eligible to receive up to $475.0 million of commercial milestones, and tiered royalties on global net sales of GSK101 – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

Previous wording

WRN Inhibitors in Tumors with High Microsatellite Instability

Current wording

IDE275 (GSK959) - WRN Inhibitor in Tumors with High Microsatellite Instability

Previous wording

A Werner Helicase Inhibitor development candidate, or DC, has been selected in collaboration with GSK. We, in collaboration with GSK, have completed the IND-enabling GLP toxicology studies and we are targeting an IND submission in the second half of 2024 to enable first-in-human clinical evaluation of Werner Helicase Inhibitor DC for patients having tumors with high MSI. Subject to IND submission and clearance, GSK will lead clinical development for the Werner Helicase program. GSK is responsible for 80% of global research and development costs and we are responsible for 20% of such costs. GSK holds a global, exclusive license to develop and commercialize the Werner Helicase Inhibitor DC.

Current wording

We, in collaboration with GSK, received IND clearance for IDE275 (GSK959), a potential first-in-class WRN inhibitor, in October 2024 to enable first-in-human clinical evaluation of IDE275 (GSK959) for patients having tumors with high MSI. GSK will lead clinical development for the Werner Helicase program. GSK is responsible for 80% of global research and development costs and we are responsible for 20% of such costs. GSK holds a global, exclusive license to develop and commercialize the Werner Helicase Inhibitor DC.

Previous wording

In October 2023, we achieved and earned a $3.0 million milestone in connection with IND-enabling studies. We have the potential to earn up to an additional $17 million aggregate milestone payments through early Phase 1 clinical studies, including $7.0 million upon IND clearance. We are also eligible to receive additional future aggregate total development milestones of up to $465.0 million. Upon commercialization, we will be eligible to receive up to $475.0 million of commercial milestones, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the Werner Helicase Inhibitor DC – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

Current wording

In October 2023, we achieved and earned a $3.0 million milestone in connection with IND-enabling studies. In October 2024, we earned a $7.0 million milestone payment for the IND clearance of IDE275 (GSK 959). We have the potential to earn up to an additional $10.0 million milestone payment upon initiation of Phase 1 clinical dose expansion. We are also eligible to receive additional future aggregate total development milestones of up to $465.0 million. Upon commercialization, we will be eligible to receive up to $475.0 million of commercial milestones, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the Werner Helicase Inhibitor DC – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

Previous wording

In July 2024, we entered into an option and license agreement with Biocytogen, pursuant to which Biocytogen granted us an option for an exclusive worldwide license from Biocytogen for a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program, or the Option. B7H3/PTK7 has been found to be co-expressed in multiple solid tumor types, including double-digit percent prevalence in lung, colorectal, and head and neck cancers, among others. Based on preclinical data, the potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program has the potential to be developed as a monotherapy agent and used in combination with multiple programs in our pipeline targeting DDR-based therapies, including our PARG inhibitor IDE161. A development candidate nomination for the B7H3/PTK7 topoisomerase-I-inhibitor payload BsADC program is targeted for the second half of 2024.

Current wording

In July 2024, we entered into an option and license agreement with Biocytogen, pursuant to which Biocytogen granted us an option for an exclusive worldwide license from Biocytogen for a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program, or the Option. B7H3/PTK7 has been found to be co-expressed in multiple solid tumor types, including double-digit percent prevalence in lung, colorectal, and head and neck cancers, among others. Based on preclinical data, the potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program has the potential to be developed as a monotherapy agent and used in combination with multiple programs in our pipeline targeting DDR-based therapies, including our PARG inhibitor IDE161. A development candidate nomination for the B7H3/PTK7 topoisomerase-I-inhibitor payload BsADC program is targeted for the fourth quarter of 2024.

Previous wording

We have initiated early preclinical research programs focused on pharmacological inhibition of several new targets, or NTs, for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures. We believe these research programs have the potential for discovery and development of first-in-class or unique-in-class or best-in-class therapeutics. We are targeting development candidate nominations in the second half of 2024 for multiple NTs, including a development candidate to treat MTAP-deletion solid tumors to enable a potential wholly-owned clinical combination with IDE397, and separately a potential first-in-class program in the KAT6 pathway. Collectively, we believe these efforts will further advance our multi-pronged clinical and business strategy. We own or control all commercial rights in our next-generation NT programs.

Current wording

We have initiated early preclinical research programs focused on pharmacological inhibition of several new targets, or NTs, for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures. We believe these research programs have the potential for discovery and development of first-in-class or unique-in-class or best-in-class therapeutics. We are targeting development candidate nominations in the fourth quarter of 2024 for multiple NTs, including a development candidate to treat MTAP-deletion solid tumors to enable a potential wholly-owned clinical combination with IDE397, and separately a development candidate for a potential first-in-class program in the KAT6 pathway. Collectively, we believe these efforts will further advance our multi-pronged clinical and business strategy. We own or control all commercial rights in our next-generation NT programs.

Previous wording

Since inception of the company, our core research has and continues to be focused on precision medicine oncology, with synthetic lethality as a central tenet. We have invested significantly and continue to invest in capabilities for identification and validation of new precision medicine targets and biomarkers for patient selection. For targets of interest, we advance our research to discover therapeutic drugs and to further qualify relevant biomarkers.

Current wording

Since the inception of the company, our core research has and continues to be focused on precision medicine oncology, with synthetic lethality as a central tenet. We have invested significantly and continue to invest in capabilities for identification and validation of new precision medicine targets and biomarkers for patient selection. For targets of interest, we advance our research to discover therapeutic drugs and to further qualify relevant biomarkers.

Previous wording

In June 2024, we were granted Small and Medium Enterprise (SME) status by the European Medicines Agency (EMA). This enables us to have access to administrative, regulatory and financial support, including fee reductions for scientific advice and regulatory procedures across all our programs.

Current wording

In June 2024, we were granted Small and Medium Enterprise, or SME, status by the European Medicines Agency, or EMA. This enables us to have access to administrative, regulatory and financial support, including fee reductions for scientific advice and regulatory procedures across all our programs.

Previous wording

During the three months ended June 30, 2024, pursuant to the January 2024 Sales Agreement, we sold an aggregate of 922,000 shares of common stock through at-the-market offerings for aggregate net proceeds of $36.5 million, after deducting underwriting discounts and commissions and other offering expenses, at a weighted average sales price of approximately $40.40 per share. As of June 30, 2024, approximately $182.1 million of common stock remained available to be sold pursuant to the January 2024 Sales Agreement.

Current wording

During the three months ended September 30, 2024, pursuant to the January 2024 Sales Agreement, we sold no shares of common stock through at-the-market offerings. As of September 30, 2024, approximately $182.1 million of common stock remained available to be sold pursuant to the January 2024 Sales Agreement.

Previous wording

We do not have any products approved for sale and have not generated any product revenue since inception. We have funded our operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK. As of June 30, 2024, we had cash, cash equivalents and marketable securities of $952.7 million, consisting primarily of money market funds, U.S. government securities, commercial paper, and corporate bonds.

Current wording

We do not have any products approved for sale and have not generated any product revenue since inception. We have funded our operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK. As of September 30, 2024, we had cash, cash equivalents and marketable securities of $1.2 billion, consisting primarily of money market funds, U.S. government securities, commercial paper, and corporate bonds.

Previous wording

Since our inception in June 2015, we have devoted substantially all of our resources to discovering and developing our product candidates. We have incurred significant operating losses to date and expect that our operating expenses will increase significantly as we advance our product candidates through preclinical and clinical development; seek regulatory approval, and prepare for, and, if approved, proceed to commercialization; acquire, discover, validate and develop additional product candidates; obtain, maintain, protect and enforce our intellectual property portfolio; and hire additional personnel. Certain program costs that contribute to our operating expenses have been and/or will be reimbursed by GSK pursuant to the GSK Collaboration Agreement, including 100% of costs we incur for research we perform in connection with the Pol Theta program and 80% of the aggregate program costs incurred by us and GSK for research each of us performs for the Werner Helicase program. We anticipate that payments which we may make to Amgen will also contribute to our operating expenses as they are reimbursed by us pursuant to the Amgen CTCSA, including 50% of external costs Amgen incurs in connection with the Amgen-sponsored and executed IDE397 / AMG 193 Combination Study. We anticipate that we will also incur costs in accordance with the Gilead CSCSA. Gilead will bear internal or external costs incurred in connection with its supply of Trodelvy. We will bear all internal and external costs and expenses associated with the conduct of the combination study. We further anticipate that we will also incur costs in accordance with the Merck CTCSA. Merck will provide KEYTRUDA for the combination study at no cost to us. We will bear all internal and external costs and expenses associated with the conduct of the combination study. In addition, we expect to incur additional costs associated with operating as a public company.

Current wording

Since our inception in June 2015, we have devoted substantially all of our resources to discovering and developing our product candidates. We have incurred significant operating losses to date and expect that our operating expenses will increase significantly as we advance our product candidates through preclinical and clinical development; seek regulatory approval, and prepare for, and, if approved, proceed to commercialization; acquire, discover, validate and develop additional product candidates; obtain, maintain, protect and enforce our intellectual property portfolio; and hire additional personnel. Certain program costs that contribute to our operating expenses have been and/or will be reimbursed by GSK pursuant to the GSK Collaboration Agreement, including 100% of costs we incur for research we perform in connection with the Pol Theta program and 80% of the aggregate program costs incurred by us and GSK for research each of us performs for the Werner Helicase program. We anticipate that payments which we may make to Amgen will also contribute to our operating expenses as they are reimbursed by us pursuant to the Amgen CTCSA, including 50% of external costs Amgen incurs in connection with the Amgen-sponsored and executed IDE397 / AMG 193 Combination Study. We anticipate that we will also incur costs in accordance with the Gilead CSCSA. Gilead will bear internal or external costs incurred in connection with its supply of Trodelvy. We will bear all internal and external costs and expenses associated with the conduct of the combination study. We further anticipate that we will also incur costs in accordance with the Merck CTCSA. Merck will provide KEYTRUDA for the study at no cost to us. We will bear all internal and external costs and expenses associated with the conduct of the study. In addition, we expect to incur additional costs associated with operating as a public company.

Previous wording

Our net losses were $92.3 million and $51.6 million for the six months ended June 30, 2024 and June 30, 2023, respectively. As of June 30, 2024, we had an accumulated deficit of $440.7 million.

Current wording

Our net losses were $144.2 million and $79.0 million for the nine months ended September 30, 2024 and September 30, 2023, respectively. As of September 30, 2024, we had an accumulated deficit of $492.5 million.

Previous wording

As of June 30, 2024, we had cash, cash equivalents, and short-term and long-term marketable securities of $952.7 million.

Current wording

As of September 30, 2024, we had cash, cash equivalents, and short-term and long-term marketable securities of $1.2 billion.

Previous wording

We believe that our cash, cash equivalents, and short-term and long-term marketable securities will be sufficient to fund our planned operations for at least twelve months from the date of the issuance of our Quarterly Report on Form 10-Q filed August 6, 2024.

Current wording

We believe that our cash, cash equivalents, and short-term and long-term marketable securities will be sufficient to fund our planned operations for at least 12 months from the date of the issuance of our Quarterly Report on Form 10-Q filed November 4, 2024.

Previous wording

To date, we have not generated any revenue from product sales, and we do not expect to generate any revenue from product sales unless and until we are able to initiate a registrational clinical trial, obtain regulatory approval and commercialize one of our product candidates in the future. Our revenue consists exclusively of collaboration revenue under the GSK Collaboration Agreement, including amounts that are recognized related to previously received upfront payments and amounts due and payable to us for research and development services. The amount of revenue recognized related to the GSK Collaboration Agreement, including as related to the previously received upfront payment or to certain development milestone payments, may vary considerably by period and certain components thereof may generally decrease year-over-year as we satisfy remaining performance obligations, for example, relating to the Pol Theta and WRN R&D Services. As of June 30, 2024, we have fully recognized the contract liabilities related to the upfront payment and reimbursements for the research and development performance obligations under the GSK Collaboration Agreement. There are no remaining contract liabilities as of June 30, 2024 as we concluded all the research and development performance obligations under the GSK Collaboration Agreement. The future revenue recognition will be contingent on additional milestone earned, profit sharing and royalties on any net product sales under our collaborations. We expect that any revenue we recognize or generate under the GSK Collaboration Agreement will fluctuate from period to period due to period to period variability in milestone payments and other payments.

Current wording

To date, we have not generated any revenue from product sales, and we do not expect to generate any revenue from product sales unless and until we are able to initiate a registrational clinical trial, obtain regulatory approval and commercialize one of our product candidates in the future. Our revenue consists exclusively of collaboration revenue under the GSK Collaboration Agreement, including amounts that are recognized related to previously received upfront payments and amounts due and payable to us for research and development services. The amount of revenue recognized related to the GSK Collaboration Agreement, including as related to the previously received upfront payment or to certain development milestone payments, may vary considerably by period and certain components thereof may generally decrease year-over-year as we satisfy remaining performance obligations, for example, relating to the Pol Theta and WRN R&D Services. As of September 30, 2024, we have fully recognized the contract liabilities related to the upfront payment and reimbursements for the research and development performance obligations under the GSK Collaboration Agreement. There are no remaining contract liabilities as of September 30, 2024 as we concluded all the research and development performance obligations under the GSK Collaboration Agreement. The future revenue recognition will be contingent on additional milestones earned, profit sharing and royalties on any net product sales under our collaborations. We expect that any revenue we recognize or generate under the GSK Collaboration Agreement will fluctuate from period to period due to period to period variability in milestone payments and other payments.

Previous wording

Substantially all of our research and development expenses consist of expenses incurred in connection with discovery and development of our product candidates. These expenses include certain payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expenses for our research and product development employees, fees to third parties to conduct certain research and development activities on our behalf including fees to CMOs and CROs in support of manufacturing and clinical activity for darovasertib, IDE397, IDE161 and WRN, consulting costs, costs for laboratory supplies, costs for product licenses and allocated overhead, including rent, equipment, depreciation, information technology costs and utilities. We expense both internal and external research and development expenses as they are incurred.

Current wording

Substantially all of our research and development expenses consist of expenses incurred in connection with the discovery and development of our product candidates. These expenses include certain payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expenses for our research and product development employees, fees to third parties to conduct certain research and development activities on our behalf including fees to CMOs and CROs in support of manufacturing and clinical activity for darovasertib, IDE397, IDE161 and WRN, consulting costs, costs for laboratory supplies, costs for product licenses and allocated overhead, including rent, equipment, depreciation, information technology costs and utilities. We expense both internal and external research and development expenses as they are incurred.

Previous wording

A discussion regarding our financial condition and results of operations for the three months ended June 30, 2024 compared to the three months ended March 31, 2024 and six months ended June 30, 2024 compared to the six months ended June 30, 2023 is presented below.

Current wording

A discussion regarding our financial condition and results of operations for the three months ended September 30, 2024 compared to the three months ended June 30, 2024 and nine months ended September 30, 2024 compared to the nine months ended September 30, 2023 is presented below.

Previous wording

Research and development expenses increased by $11.7 million, or 27%, during the three months ended June 30, 2024 compared to the three months ended March 31, 2024 due to an increase of $8.2 million primarily driven by fees paid to CROs, CMOs and consultants related to the advancement of our lead product candidates through preclinical and clinical studies, increase in $2.3 million in personnel-related expenses, including stock-based compensation and salaries and benefits to support our growth, and an increase in $1.2 million in costs for laboratory supplies, facilities and software to support our research and development programs.

Current wording

Research and development expenses increased by $2.6 million, or 5%, during the three months ended September 30, 2024 compared to the three months ended June 30, 2024 due to an increase of $2.1 million primarily driven by fees paid to CROs, CMOs and consultants related to the advancement of our lead product candidates through preclinical and clinical studies and an increase of $0.9 million related to facility expenses, partially offset by a decrease of $0.4 million in costs for laboratory supplies.

Previous wording

Interest income increased by $0.7 million, or 6%, during the three months ended June 30, 2024 compared to the three months ended March 31, 2024, primarily due to higher investment balances and interest rates.

Current wording

Interest income increased by $2.9 million, or 24%, during the three months ended September 30, 2024 compared to the three months ended June 30, 2024, primarily due to higher investment balances.