Zentalis Pharmaceuticals Inc

Previous wording

We are a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers. Our lead product candidate, azenosertib (ZN-c3), is a potentially first-in-class and best-in-class WEE1 inhibitor for advanced solid tumors and hematological malignancies. Azenosertib is being evaluated as a monotherapy and in combination across multiple ongoing clinical trials. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types and in combination with several chemotherapy backbones. As part of our azenosertib clinical development program, we are exploring enrichment strategies targeting tumors with high levels of replication stress, such as Cyclin E1 positive tumors, homologous recombination deficient tumors, and tumors with oncogenic driver mutations. We currently exclusively in-license or solely own worldwide development and commercialization rights to azenosertib.

Current wording

We are a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers. Our lead product candidate, azenosertib (ZN-c3), is a potentially first-in-class and best-in-class WEE1 inhibitor for advanced solid tumors. Azenosertib is being evaluated as a monotherapy and in combination across multiple ongoing clinical trials. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types and in combination with several chemotherapy backbones. As part of our azenosertib clinical development program, we are exploring enrichment strategies targeting tumors with high levels of replication stress, such as Cyclin E1 positive tumors, homologous recombination deficient tumors, and tumors with oncogenic driver mutations. We currently exclusively in-license or solely own worldwide development and commercialization rights to azenosertib.

Previous wording

Azenosertib is a potentially best-in-class and first-in-class oral, small molecule WEE1 inhibitor. The inhibition of WEE1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death and thereby preventing tumor growth and potentially causing tumor regression. Currently, there are no WEE1 inhibitors approved by the FDA. We have designed azenosertib to have advantages over other investigational therapies targeting WEE1, including superior selectivity and pharmacokinetic, or PK, properties. Azenosertib is currently being evaluated in the clinic for advanced solid tumors and hematological malignancies as a monotherapy, in combination with traditional chemotherapy and other DNA damaging agents, and in combination with molecularly targeted agents. On June 18, 2024, we disclosed that the FDA placed our ZN-c3-001, TETON (ZN-c3-004) and DENALI (ZN-c3-005) trials on partial clinical hold following two deaths in the DENALI trial due to presumed sepsis. We have been working closely with the FDA to resolve the partial clinical hold as quickly as possible. In the course of our dialogue with the FDA, the FDA also placed ZN-c3-002 on partial clinical hold. ZN-c3-002, which currently has four patients on active treatment, is under the same IND as ZN-c3-001, TETON and DENALI. Patients currently enrolled in the studies on partial clinical hold may continue to receive azenosertib, although no additional patients may be enrolled until the partial clinical hold is resolved. We previously disclosed that we are targeting the submission of our first NDA for azenosertib in a gynecologic malignancy in 2026—as disclosed on June 18, 2024, we plan to provide updates on the azenosertib clinical development timelines following resolution of the partial clinical hold.

Current wording

Azenosertib is a potentially best-in-class and first-in-class oral, small molecule WEE1 inhibitor. The inhibition of WEE1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death and thereby preventing tumor growth and potentially causing tumor regression. Currently, there are no WEE1 inhibitors approved by the FDA. We have designed azenosertib to have advantages over other investigational therapies targeting WEE1, including superior selectivity and pharmacokinetic, or PK, properties. Azenosertib is currently being evaluated in the clinic for advanced solid tumors as a monotherapy, in combination with traditional chemotherapy and other DNA damaging agents, and in combination with molecularly targeted agents. On June 18, 2024, we disclosed that the FDA had placed certain of our azenosertib clinical trials on partial clinical hold following two deaths in the DENALI (ZN-c3-005) trial due to presumed sepsis. On September 16, 2024, we announced that the FDA had lifted the partial clinical hold and that the FDA had cleared us to resume enrollment in all ongoing azenosertib clinical studies with no changes in the clinical development plan. In January 2025, we plan to host an investor event, where we will share updated azenosertib clinical data and a regulatory update, including plans for registration-intent studies.

Previous wording

•Clinical Trial of Azenosertib in Platinum Sensitive Ovarian Cancer (PSOC). We previously disclosed plans to initiate a clinical trial evaluating azenosertib in PSOC patients in the first-line maintenance setting in 2025 as well as to disclose additional details about this trial in the second half of 2024—as disclosed on June 18, 2024, we plan to provide updates on the azenosertib clinical development timelines following resolution of the partial clinical hold.

Current wording

•Clinical Trial of Azenosertib in Platinum Sensitive Ovarian Cancer (PSOC). We previously disclosed plans to initiate a clinical trial evaluating azenosertib in PSOC patients in the first-line maintenance setting.

Previous wording

•Monotherapy - Phase 2 Clinical Trial in Cyclin E1 Driven High-Grade Serous Ovarian Cancer, Fallopian Tube, or Primary Peritoneal Cancer (HGSOC) (DENALI - ZN-c3-005). We are evaluating azenosertib as a monotherapy in a Phase 2 clinical trial in patients with Cyclin E1 positive platinum resistant HGSOC. Our Cyclin E1 positive enrichment strategy is supported by preclinical data that showed that high Cyclin E1 protein expression sensitized cancer cells to the anti-tumor effects of azenosertib as well as preliminary retrospective clinical data that Cyclin E1 protein levels may be associated with clinical benefit from WEE1 inhibition. In addition, in April 2023, we announced preclinical data at the 2023 American Association for Cancer Research, or AACR, Annual Meeting that demonstrated that azenosertib drove cancer cell death in Cyclin E1-high tumor cellsin vitro and substantially inhibited growth of Cyclin E1-high, patient derived, in vivo tumor models. On June 18, 2024, we disclosed that we had completed enrollment of Cohort 1b of this trial after enrolling over 100 patients and that we plan to disclose topline results from Cohort 1b of this trial in the second half of 2024.

Current wording

•Monotherapy - Phase 2 Clinical Trial in Cyclin E1 Driven High-Grade Serous Ovarian Cancer, Fallopian Tube, or Primary Peritoneal Cancer (HGSOC) (DENALI - ZN-c3-005). We are evaluating azenosertib as a monotherapy in a Phase 2 clinical trial in patients with Cyclin E1 positive platinum resistant HGSOC. Our Cyclin E1 positive enrichment strategy is supported by preclinical data that showed that high Cyclin E1 protein expression sensitized cancer cells to the anti-tumor effects of azenosertib as well as preliminary retrospective clinical data that Cyclin E1 protein levels may be associated with clinical benefit from WEE1 inhibition. In addition, in April 2023, we announced preclinical data at the 2023

Previous wording

•Monotherapy/Combination - Phase 1/2 Clinical Trial of Azenosertib as a Monotherapy and with PARP Inhibitor (PARPi) in Platinum Resistant Ovarian Cancer (PROC) (MAMMOTH - ZN-c3-006). We are evaluating azenosertib as a monotherapy and in combination with GSK plc’s, or GSK’s, PARP inhibitor, niraparib (ZEJULA®), in a Phase 1/2 clinical trial in PROC patients who have failed PARPi treatment as part of a clinical collaboration with GSK. This clinical study is supported by preclinical data that showed that combining azenosertib and niraparib resulted in synergistic cell killing in ovarian cancerin vivo models. As we reiterated on June 18, 2024, we plan to disclose topline data from this trial in the second half of 2024.

Current wording

•Monotherapy/Combination - Phase 1/2 Clinical Trial of Azenosertib as a Monotherapy and with PARP Inhibitor (PARPi) in Platinum Resistant Ovarian Cancer (PROC) (MAMMOTH - ZN-c3-006). We have evaluated azenosertib as a monotherapy and in combination with GSK plc’s, or GSK’s, PARP inhibitor, niraparib (ZEJULA®), in a Phase 1/2 clinical trial in PROC patients who have progressed on PARPi treatment as part of a clinical collaboration with GSK. This clinical study is supported by preclinical data that showed that combining azenosertib and niraparib resulted in synergistic cell killing in ovarian cancerin vivo models.

Previous wording

•Monotherapy - Phase 2 Clinical Trial in Recurrent or Persistent Uterine Serous Carcinoma (USC) (TETON - ZN-c3-004). Azenosertib is currently being evaluated as a monotherapy in a Phase 2 clinical trial in patients with USC. As of a September 14, 2022 data cutoff, a total of 43 patients were enrolled and dosed. Azenosertib was well tolerated. The most common treatment related adverse events, or TRAEs, were nausea (60.5% all grades/9.3% grade 3 or higher), fatigue (46.5% all grades/9.3% grade 3 or higher), diarrhea (37.2% all grades/7.0% grade 3 or higher) and vomiting (32.6% all grades/7.0% grade 3 or higher). The FDA granted Fast Track designation in November 2021 to azenosertib in patients with advanced or metastatic USC who have received at least one prior platinum-based chemotherapy regimen for management of advanced or metastatic disease. We believe that the study design in this patient population has the potential to support registration in the United States. We previously disclosed that we expect to disclose topline data from this trial in the second half of 2025—as disclosed on June 18, 2024, we plan to provide updates on certain of the azenosertib data timelines following resolution of the partial clinical hold.

Current wording

•Monotherapy - Phase 2 Clinical Trial in Recurrent or Persistent Uterine Serous Carcinoma (USC) (TETON - ZN-c3-004). Azenosertib is currently being evaluated as a monotherapy in a Phase 2 clinical trial in patients with USC. As of a September 14, 2022 data cutoff, a total of 43 patients were enrolled and dosed. Azenosertib was well tolerated. The most common treatment related adverse events, or TRAEs, were nausea (60.5% all grades/9.3% grade 3 or higher), fatigue (46.5% all grades/9.3% grade 3 or higher), diarrhea (37.2% all grades/7.0% grade 3 or higher) and vomiting (32.6% all grades/7.0% grade 3 or higher). The FDA granted Fast Track designation in November 2021 to azenosertib in patients with advanced or metastatic USC who have received at least one prior platinum-based chemotherapy regimen for management of advanced or metastatic disease. We believe that the study design in this patient population has the potential to support registration in the United States.

Previous wording

•Combination - Phase 1b Clinical Trial of Azenosertib and Chemotherapy in PROC (ZN-c3-002). Azenosertib is currently being evaluated in combination with each of paclitaxel, carboplatin, PLD, and gemcitabine in four separate cohorts in a Phase 1b clinical trial in patients with PROC. On May 25, 2023, we announced positive data from this Phase 1b clinical trial. Azenosertib was well tolerated in combination with multiple types of chemotherapy and demonstrated encouraging clinical activity, with noteworthy objective response rates, or ORRs, and median progression free survival, or mPFS, in all patients, but especially in those patients with Cyclin E1 positive tumors, a subgroup recognized to have a poor prognosis and to show relatively poor outcomes following treatment with chemotherapy. A total of 115 patients were enrolled in the study across all chemotherapy combination groups. At April 10, 2023, 94 were response evaluable. Across all dosing schedules, azenosertib plus paclitaxel demonstrated the highest ORR of 50.0% (mPFS of 7.4m; mDOR of 5.6m), followed by an ORR of 38.5% (mPFS of 8.3m; mDOR of 6.2m) for azenosertib plus gemcitabine. Azenosertib plus carboplatin demonstrated an ORR of 35.7% (mPFS of 10.4m; mDOR of 11.4m), and azenosertib plus PLD demonstrated an ORR of 19.4% (mPFS of 6.3m; mDOR of 8.3m). Of patients who had available tissue for immunohistochemistry, or IHC, 87% were Cyclin E1+ (H-score >50). Cyclin E1+ status was associated with a superior ORR and a longer mPFS across the response-evaluable patient population with IHC data (ORR of 40.0% vs 8.3%; mPFS of 9.86 vs 3.25 months; HR = 0.37; P = 0.0078), showcasing the potential synergy of WEE1 inhibition with chemotherapy in this patient population. Frequent Grade ≥3 TRAEs (%) across all azenosertib intermittent dosing groups were thrombocytopenia (27.5%), neutropenia (25.5%), anemia (15.7%), and fatigue (9.8%).

Current wording

•Combination - Phase 1b Clinical Trial of Azenosertib and Chemotherapy in PROC (ZN-c3-002). Azenosertib has been evaluated in combination with each of paclitaxel, carboplatin, PLD, and gemcitabine in four separate cohorts in a Phase 1b clinical trial in patients with PROC. On May 25, 2023, we announced positive data from this Phase 1b clinical trial. Azenosertib was well tolerated in combination with multiple types of chemotherapy and demonstrated encouraging clinical activity, with noteworthy objective response rates, or ORRs, and median progression free survival, or mPFS, in all patients, but especially in those patients with Cyclin E1 positive tumors, a subgroup recognized to have a poor prognosis and to show relatively poor outcomes following treatment with chemotherapy. A total of 115 patients were enrolled in the study across all chemotherapy combination groups. At April 10, 2023, 94 were response evaluable. Across all dosing schedules, azenosertib plus paclitaxel demonstrated the highest ORR of 50.0% (mPFS of 7.4m; mDOR of 5.6m), followed by an ORR of 38.5% (mPFS of 8.3m; mDOR of 6.2m) for azenosertib plus gemcitabine. Azenosertib plus carboplatin demonstrated an ORR of 35.7% (mPFS of 10.4m; mDOR of 11.4m), and azenosertib plus PLD demonstrated an ORR of 19.4% (mPFS of 6.3m; mDOR of 8.3m). Of patients who had available tissue for immunohistochemistry, or IHC, 87% were Cyclin E1+ (H-score >50). Cyclin E1+ status was associated with a superior ORR and a longer mPFS across the response-evaluable patient population with IHC data (ORR of 40.0% vs 8.3%; mPFS of 9.86 vs 3.25 months; HR = 0.37; P = 0.0078), showcasing the potential synergy of WEE1 inhibition with chemotherapy in this patient population. Frequent Grade ≥3 TRAEs (%) across all azenosertib intermittent dosing groups were thrombocytopenia (27.5%), neutropenia (25.5%), anemia (15.7%), and fatigue (9.8%).

Previous wording

•Monotherapy - Phase 1b Dose Finding Clinical Trial in Solid Tumors (ZN-c3-001). We are currently evaluating azenosertib as a monotherapy in a Phase 1b dose finding clinical trial for the treatment of solid tumors. On June 6, 2023, we announced positive data from this clinical trial. As of April 24, 2023, a total of 127 heavily pretreated patients with advanced solid tumors were enrolled and received monotherapy azenosertib at doses ≥ 300 mg on either continuous daily dosing or intermittent weekly administration schedules. Across all tumor types, 74 patients received azenosertib on a continuous dosing schedule and 53 patients received azenosertib on an intermittent dosing schedule. When evaluating continuous versus intermittent at comparable clinically meaningful dose levels, the data were the following: intermittent dosing maintained safety and improved tolerability of azenosertib as compared to continuous dosing. Gastrointestinal, fatigue, and hematologic Grade 3 and 4 TRAEs were comparable or favorable versus continuous dosing. No discontinuations due to TRAEs were observed in the intermittent cohorts. Steady state exposure, as measured by AUC 0-24, more than doubled at the intermittent dose of 400 mg, 5 days on, 2 days off, compared to AUC observed at 300 mg daily with continuous administration, and intermittent dosing achieved higher maximal concentration levels as compared to continuous administration. As of June 2, 2023, the confirmed ORR in the combined ovarian and USC subgroup of patients treated with intermittent dosing was 36.8% (7/19), versus 19.2% (5/26) in those who received a continuous dosing. In the response evaluable patients who received intermittent dosing azenosertib, the confirmed ORR was 50% in USC and 30.8% in ovarian cancer. 89% of ovarian cancer and USC patients who received an intermittent dosing schedule had target lesion reductions from their baseline scans. Patients in this subgroup who received an intermittent dosing schedule had a median follow up of 4.4 months, and 63% (12/19) patients remained on therapy as of June 2, 2023. On November 6, 2023, we announced updated data from this trial. Data from October 25, 2023 in the same population of patients (ovarian cancer and USC patients) that were response-evaluable on June 2, 2023, showed that there continued to be a 36.8% (7/19) ORR in these patients. As compared to the June 2, 2023 data, the median follow-up for patients in this subgroup increased to 9.2 months and the mPFS increased to 6.5 months. As of September 27, 2023, azenosertib continued to demonstrate a favorable safety and tolerability profile with additional safety-evaluable patients and longer follow-up. As we reiterated on June 18, 2024, we plan to disclose the final results from this trial in the second half of 2024.

Current wording

•Monotherapy - Phase 1b Dose Finding Clinical Trial in Solid Tumors (ZN-c3-001). We have evaluated azenosertib as a monotherapy in a Phase 1b dose finding clinical trial for the treatment of solid tumors. On June 6, 2023, we announced positive data from this clinical trial. As of April 24, 2023, a total of 127 heavily pretreated patients with advanced solid tumors were enrolled and received monotherapy azenosertib at doses ≥ 300 mg on either continuous daily dosing or intermittent weekly administration schedules. Across all tumor types, 74 patients received azenosertib on a continuous dosing schedule and 53 patients received azenosertib on an intermittent dosing schedule. When evaluating continuous versus intermittent at comparable clinically meaningful dose levels, the data were the following: intermittent dosing maintained safety and improved tolerability of azenosertib as compared to continuous dosing. Gastrointestinal, fatigue, and hematologic Grade 3 and 4 TRAEs were comparable or favorable versus continuous dosing. No discontinuations due to TRAEs were observed in the intermittent cohorts. Steady state exposure, as measured by AUC 0-24, more than doubled at the intermittent dose of 400 mg, 5 days on, 2 days off, compared to AUC observed at 300 mg daily with continuous administration, and intermittent dosing achieved higher maximal concentration levels as compared to continuous administration. As of June 2, 2023, the confirmed ORR in the combined ovarian and USC subgroup of patients treated with intermittent dosing was 36.8% (7/19), versus 19.2% (5/26) in those who received a continuous dosing. In the response evaluable patients who received intermittent dosing azenosertib, the confirmed ORR was 50% in USC and 30.8% in ovarian cancer. 89% of ovarian cancer and USC patients who received an intermittent dosing schedule had target lesion reductions from their baseline scans. Patients in this subgroup who received an intermittent dosing schedule had a median follow up of 4.4 months, and 63% (12/19) patients remained on therapy as of June 2, 2023. On November 6, 2023, we announced updated data from this trial. Data from October 25, 2023 in the same population of patients (ovarian cancer and USC patients) that were response-evaluable on June 2, 2023, showed that there continued to be a 36.8% (7/19) ORR in these patients. As compared to the June 2, 2023 data, the median follow-up for patients in this subgroup increased to 9.2 months and the mPFS increased to 6.5 months. As of September 27, 2023, azenosertib continued to demonstrate a favorable safety and tolerability profile with additional safety-evaluable patients and longer follow-up.

Previous wording

Thirty-one patients were enrolled in the study, of which 31 were evaluable for safety, 29 were evaluable for dose-limiting toxicities and 28 were evaluable for efficacy. The median age was 27 (range 12-76) and 21 patients (68%) were ≤39 years old. Patients received a median of 3 (range 1-9) prior therapies, including 10 patients (32%) who had previous treatment with gemcitabine. The 18-week event-free survival rate, or EFS, which was defined as time from treatment initiation until disease progression or death due to any cause, was 39% (11/28) across all dose levels. The EFS observed in the study compares favorably to historical cohorts with a similar patient population where a 16-week EFS of approximately 12% has been reported. The maximum tolerated dose, or MTD, of azenosertib was determined to be 150 mg daily on a 5:2 schedule (5 days on, 2 days off) plus gemcitabine 800 mg/m 2. At the MTD, the most frequent Grade ≥3 adverse events (≥20%) included thrombocytopenia and lymphopenia (33% each); there were no Grade 4 thrombocytopenia events or instances of febrile neutropenia at the MTD. Data support further investigation of azenosertib administered in combination with gemcitabine in patients with relapsed or refractory osteosarcoma in an upcoming investigator-initiated Phase 2 trial. As previously disclosed, we received orphan drug designation and rare pediatric disease designation from the FDA for azenosertib in osteosarcoma.

Current wording

•Combination - Phase 1 Clinical Trial of Azenosertib and Chemotherapy in Relapsed or Refractory Osteosarcoma (ZN-c3-003). We disclosed the final results from this trial in May 2024, which were subsequently presented in a poster at the 2024 American Society of Clinical Oncology Annual Meeting. Thirty-one patients were enrolled in the study, of which 31 were evaluable for safety, 29 were evaluable for dose-limiting toxicities and 28 were evaluable for efficacy. The median age was 27 (range 12-76) and 21 patients (68%) were ≤39 years old. Patients received a median of 3 (range 1-9) prior therapies, including 10 patients (32%) who had previous treatment with gemcitabine. The 18-week event-free survival rate, or EFS, which was defined as time from treatment initiation until disease progression or death due to any cause, was 39% (11/28) across all dose levels. The EFS observed in the study compares favorably to historical cohorts with a similar patient population where a 16-week EFS of approximately 12% has been reported. The maximum tolerated dose, or MTD, of azenosertib was determined to be 150 mg daily on a 5:2 schedule (5 days on, 2 days off) plus gemcitabine 800 mg/m 2. At the MTD, the most frequent Grade ≥3 adverse events (≥20%) included thrombocytopenia and lymphopenia (33% each); there were no Grade 4 thrombocytopenia events or instances of febrile neutropenia at the MTD. Data support further investigation of azenosertib administered in combination with gemcitabine in patients with relapsed or refractory osteosarcoma in an upcoming investigator-initiated Phase 2 trial. As previously disclosed, we received orphan drug designation and rare pediatric disease designation from the FDA for azenosertib in osteosarcoma.

Previous wording

•Combination - Phase 1/2 Clinical Trial of Azenosertib with Encorafenib and Cetuximab (BEACON Regimen) in BRAF V600E Mutant Metastatic Colorectal Cancer (mCRC) (ZN-c3-016). We are collaborating with Pfizer Inc., or Pfizer, to evaluate azenosertib in combination with encorafenib and cetuximab, an FDA-approved standard of care known as the BEACON regimen, in patients with BRAF V600E mutant mCRC in a Phase 1/2 clinical trial. In preclinical studies, WEE1 inhibition has shown synergy with many targeted agents in mutationally driven cancers, and the addition of azenosertib to the BEACON regimen enhanced anti-tumor activity in a cell-line-derived xenograft model. We initiated enrollment in this clinical trial in the first quarter of 2023, and expect to disclose the initial data from this trial in the second half of 2024.

Current wording

•Combination - Phase 1/2 Clinical Trial of Azenosertib with Encorafenib and Cetuximab (BEACON Regimen) in BRAF V600E Mutant Metastatic Colorectal Cancer (mCRC) (ZN-c3-016). We are collaborating with Pfizer Inc., or Pfizer, to evaluate azenosertib in combination with encorafenib and cetuximab, an FDA-approved standard of care known as the BEACON regimen, in patients with BRAF V600E mutant mCRC in a Phase 1/2 clinical trial. In preclinical studies, WEE1 inhibition has shown synergy with many targeted agents in mutationally driven cancers, and the addition of azenosertib to the BEACON regimen enhanced anti-tumor activity in a cell-line-derived xenograft model. We initiated enrollment in this clinical trial in the first quarter of 2023.

Previous wording

Since inception, we have incurred significant operating losses. Our net loss was $292.3 million for the year ended December 31, 2023. We had a net loss of $78.2 million and $175.8 million for the six months ended June 30, 2024 and June 30, 2023, respectively. We had an accumulated deficit of $966.8 million as of June 30, 2024. We expect to continue to incur significant expenses and operating losses for the foreseeable future. We had cash, cash equivalents and marketable securities of $426.4 million as of June 30, 2024, which includes $27.8 million representing the June 30, 2024 fair value of Immunome common stock received by the Company as part of its upfront payment for the out-licensing of its ROR1 antibody-drug conjugate (ADC) product candidate and ADC platform in January 2024. We believe that our existing cash, cash equivalents and marketable securities as of June 30, 2024 will be sufficient to fund our operating expenses and capital expenditure requirements into mid-2026. We have based these estimates on assumptions that may prove to be imprecise, and we could utilize our available capital resources sooner than we expect.

Current wording

Since inception, we have incurred significant operating losses. Our net loss was $292.3 million for the year ended December 31, 2023. We had a net loss of $118.4 million and $231.4 million for the nine months ended September 30, 2024 and September 30, 2023, respectively. We had an accumulated deficit of $1.0 billion as of September 30, 2024. We expect to continue to incur significant expenses and operating losses for the foreseeable future. We had cash, cash equivalents and marketable securities of $391.3 million as of September 30, 2024. We believe that our existing cash, cash equivalents and marketable securities as of September 30, 2024 will be sufficient to fund our operating expenses and capital expenditure requirements into mid-2026. We have based these estimates on assumptions that may prove to be imprecise, and we could utilize our available capital resources sooner than we expect.

Previous wording

In April 2021, we entered into a clinical trial collaboration and supply agreement with GSK under which we are evaluating the combination of azenosertib and niraparib, GSK’s poly (ADP-ribose) polymerase (PARP) inhibitor, in patients with PROC. Pursuant to this agreement, we are responsible for the conduct and cost of the relevant studies, under the supervision of a joint development committee made up of our representatives and representatives of GSK that meets quarterly. GSK is supplying niraparib for use in the collaboration, at no cost to us. We are required to provide to GSK clinical data and other reports upon completion of the study.

Current wording

In April 2021, we entered into a clinical trial collaboration and supply agreement with GSK under which we have evaluated the combination of azenosertib and niraparib, GSK’s poly (ADP-ribose) polymerase (PARP) inhibitor, in patients with PROC. Pursuant to this agreement, we are responsible for the conduct and cost of the relevant studies, under the supervision of a joint development committee made up of our representatives and representatives of GSK that meets quarterly. GSK is supplying niraparib for use in the collaboration, at no cost to us. We are required to provide to GSK clinical data and other reports upon completion of the study.

Previous wording

In January 2024, we entered into an exclusive, worldwide license agreement with Immunome, under which Immunome licensed from us ZPC-21 (now known as IM-1021), a preclinical ROR1 ADC with best-in-class potential, and our proprietary ADC platform technology. Under the terms of the deal, we received an up-front payment of $35 million in cash and Immunome common stock (with the stock valued at the trailing 30-day volume-weighted average price). We are eligible to receive up to $275 million of milestone payments for ZPC-21 and other products that utilize the licensed platform technology in addition to mid-to-high single-digit royalties.

Current wording

In January 2024, we entered into an exclusive, worldwide license agreement with Immunome, or the Immunome License Agreement, under which Immunome licensed from us ZPC-21 (now known as IM-1021), a preclinical ROR1 ADC with best-in-class potential, and our proprietary ADC platform technology, or the ADC Assets. Under the terms of the deal, we received an up-front payment of $35 million in cash and Immunome common stock (with the stock valued at the trailing 30-day volume-weighted average price). In October 2024, we entered into an asset purchase agreement with Immunome, pursuant to which Immunome purchased the ADC Assets, or the Immunome Purchase Agreement. We received approximately 1.8 million shares of Immunome common stock, which was valued at approximately $21.9 million on the date of acquisition. We are also eligible to receive $5.0 million of contingent consideration upon the achievement of a developmental milestone. The Immunome License Agreement terminated upon the parties’ entry into the Immunome Purchase Agreement.

Previous wording

Research and development, or R&D, expenses for the three months ended June 30, 2024 were $48.4 million, compared to $42.7 million for the three months ended June 30, 2023. The increase of $5.7 million was primarily due to increases of $7.4 million for clinical and certain translational expenses and $1.0 million for drug manufacturing and supplies costs. We also saw increases of $1.4 million from no R&D cost sharing with Zentera. These increases were partially offset by a decrease of $2.7 million of personnel expense of which $1.5 million is related to non-cash stock-based compensation and $1.4 million of facilities and allocated expenses.

Current wording

Research and development, or R&D, expenses for the three months ended September 30, 2024 were $36.8 million, compared to $46.8 million for the three months ended September 30, 2023. The decrease of $9.9 million was primarily due to decreases of $5.8 million for clinical and certain translational expenses, $2.3 million for drug manufacturing and R&D supplies, and $0.8 million for consulting, in addition to a net decrease of $1.8 million related to personnel expense. These decreases were partially offset by net increases of $0.8 million of facilities, allocated and other expenses.

Previous wording

General and administrative expenses for the three months ended June 30, 2024 were $16.8 million, compared to $15.7 million during the three months ended June 30, 2023. This increase of $1.1 million was primarily attributable to an increase in personnel expenses of $1.3 million and lease termination costs of $0.5 million. This was partially offset by a decrease of other expenses of $0.7 million, net.

Current wording

General and administrative expenses for the three months ended September 30, 2024 were $14.6 million, compared to $15.9 million during the three months ended September 30, 2023. This decrease of $1.3 million was primarily attributable to decreases of $1.1 million of consulting and outside services expense and $0.4 million of overhead and allocated expenses. This was partially offset by a net increase of $0.2 million related to personnel expense.

Previous wording

Investment and other income (expense), net was $(22.9) million for the three months ended June 30, 2024, compared to $4.5 million for the three months ended June 30, 2023. The decrease of $27.3 million was primarily driven by decreases in the fair value of Immunome stock for $28.9 million offset by an increase of $1.1 million in returns on invested cash and marketable securities and decreases of other miscellaneous expenses of $0.5 million.

Current wording

Investment and other income (expense), net was $11.2 million for the three months ended September 30, 2024, compared to $7.2 million for the three months ended September 30, 2023. The increase of $4.0 million was primarily driven by increases in the fair value of Immunome stock of $5.7 million and decrease of other miscellaneous, net expenses of $0.1 million. This was offset by a decrease of $1.8 million in returns on invested cash and marketable securities.

Previous wording

We did not record a loss on equity method investment for the three months ended June 30, 2024. We recorded a loss on equity investment of $13.7 million for the three months ended June 30, 2023, related to the divestment of our equity method investment.

Current wording

We did not record a loss on equity method investment for the three months ended September 30, 2024 and 2023.

Previous wording

License revenue for the six months ended June 30, 2024, was $40.6 million compared to zero for the six months ended June 30, 2023. The increase relates to the License Agreement with Immunome entered during the three months ended March 31, 2024.

Current wording

License revenue for the nine months ended September 30, 2024, was $40.6 million compared to zero for the nine months ended September 30, 2023. The increase relates to the License Agreement with Immunome entered during the three months ended March 31, 2024.

Previous wording

R&D expenses for the six months ended June 30, 2024 were $98.0 million, compared to $91.3 million for the six months ended June 30, 2023. The increase of $6.7 million was primarily due to increases of $10.2 million for clinical and certain translational expenses and $3.3 million for drug manufacturing costs, respectively. We also saw increases of $3.5 million from no R&D cost sharing with Zentera. These increases were partially offset by decreases of $6.1 million in facilities and overhead allocations, $3.0 million of personnel expenses and $1.2 million of other expenses, net.

Current wording

R&D expenses for the nine months ended September 30, 2024 were $134.8 million, compared to $138.0 million for the nine months ended September 30, 2023. The decrease of $3.2 million was primarily due to decreases of $4.9 million related to personnel expense, $4.5 million of allocated overhead expenses and $1.5 million of consulting and outside services. Additionally, expenses decreased by $0.2 million for drug manufacturing and related freight costs. These decreases were offset by increases of $4.4 million for clinical and certain translational expenses and $3.5 million from no R&D cost sharing with Zentera.

Previous wording

Zentera In-process Research and Development expenses for the three months ended June 30, 2024 were zero, compared to $45.6 million for the three months ended June 30, 2023. The decrease was due to $45.6 million of total cash and non-cash consideration transferred to Zentera for in-process research and development during the three months ended June 30, 2023 relating to the termination of our collaboration with Zentera.

Current wording

Zentera In-process Research and Development expenses for the nine months ended September 30, 2024 were zero, compared to $45.6 million for the nine months ended September 30, 2023. The decrease was due to $45.6 million of total cash and non-cash consideration transferred to Zentera for in-process research and development during the nine months ended September 30, 2023 relating to the termination of our collaboration with Zentera.

Previous wording

Investment and other income, net was $12.1 million for the six months ended June 30, 2024, compared to $8.6 million for the six months ended June 30, 2023. The increase of $3.5 million was primarily driven by increases in the fair value of Immunome stock of $2.3 million, an increase of $3.4 million in returns on invested cash and marketable securities and $0.7 million of income from the sublease of our New York office. These amounts were partially offset by transaction and other miscellaneous expenses.

Current wording

Investment and other income, net was $23.3 million for the nine months ended September 30, 2024, compared to $15.8 million for the nine months ended September 30, 2023. The increase of $7.6 million was primarily driven by increases in the fair value of Immunome stock of $7.9 million, an increase of $0.9 million in returns on invested cash and marketable securities and $0.2 million of income from the sublease of our New York office. These amounts were partially offset by transaction and other miscellaneous expenses.

Previous wording

We did not record a loss on equity method investment for the six months ended June 30, 2024. We recorded a loss on equity investment of $16.0 million for the three months ended June 30, 2023, related to the divestment of our equity method investment.

Current wording

We did not record a loss on equity method investment for the nine months ended September 30, 2024. We recorded a loss on equity method investment of $16.0 million for the nine months ended September 30, 2023, related to the divestment of our equity method investment.

Previous wording

We do not currently have any approved products and have never generated any revenue from product sales. To date, we have financed our operations primarily through the sale of equity securities. From inception through June 30, 2024, we raised a total of $1.2 billion in gross proceeds from the sale of shares of our common stock and convertible preferred units. As of June 30, 2024, we had $37.0 million in cash and cash equivalents, $389.4 million in marketable securities, and an accumulated deficit of $966.8 million. We maintain the majority of our cash and cash equivalents in accounts with major financial institutions, and our deposits at these institutions exceed insured limits. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our business and financial position. We had no indebtedness as of June 30, 2024.

Current wording

We do not currently have any approved products and have never generated any revenue from product sales. To date, we have financed our operations primarily through the sale of equity securities. From inception through September 30, 2024, we raised a total of $1.2 billion in gross proceeds from the sale of shares of our common stock and convertible preferred units. As of September 30, 2024, we had $41.3 million in cash and cash equivalents, $349.9 million in marketable securities, and an accumulated deficit of $1.0 billion. We maintain the majority of our cash and cash equivalents in accounts with major financial institutions, and our deposits at these institutions exceed insured limits. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our business and financial position. We had no indebtedness as of September 30, 2024.

Previous wording

Net cash used in operating activities for the six months ended June 30, 2024 was $87.1 million, consisting primarily of our net loss of $78.2 million as we incurred expenses associated with research and development activities for our product candidates and incurred general and administrative expenses, as well as changes in operating assets and liabilities of $2.2 million, partially offset by non-cash adjustments of $6.7 million.

Current wording

Net cash used in operating activities for the nine months ended September 30, 2024 was $131.2 million, consisting primarily of our net loss of $118.4 million as we incurred expenses associated with research and development activities for our product candidates and incurred general and administrative expenses, as well as changes in operating assets and liabilities of $9.5 million and by non-cash adjustments of $3.3 million.

Previous wording

Net cash used in operating activities for the six months ended June 30, 2023 was $128.6 million, consisting primarily of our net loss of $175.8 million as we incurred expenses associated with research and development activities for our product candidates and incurred general and administrative expenses, and offset by non-cash adjustments of $56.4 million and changes in operating assets and liabilities of $9.2 million.

Current wording

Net cash used in operating activities for the nine months ended September 30, 2023 was $167.2 million, consisting primarily of our net loss of $231.4 million as we incurred expenses associated with research and development activities for our product candidates and incurred general and administrative expenses, and offset by non-cash adjustments of $68.6 million and changes in operating assets and liabilities of $4.4 million.

Previous wording

Net cash provided by investing activities for the six months ended June 30, 2024 of $96.0 million was attributable to proceeds of maturities of marketable securities of $125.7 million, offset by net investment of excess cash of $29.5 million, purchases of property and equipment of $221 thousand and proceeds from sales of property and equipment of $65 thousand.

Current wording

Net cash provided by investing activities for the nine months ended September 30, 2024 of $144.3 million was attributable to proceeds of maturities of marketable securities of $199.7 million and the sale of marketable securities of $33.5 million, offset by net investment of excess cash of $88.7 million, purchases of property and equipment of $221 thousand and proceeds from sales of property and equipment of $65 thousand.

Previous wording

Net cash provided by investing activities for the six months ended June 30, 2023 of $115.1 million was attributable to the proceeds from maturities of marketable securities of $304.5 million, offset by net investment of excess cash of $189.1 million and purchases of property and equipment of $319 thousand.

Current wording

Net cash used in investing activities for the nine months ended September 30, 2023 of $2.4 million was attributable to the proceeds from maturities of marketable securities of $451.2 million, offset by net investment of excess cash of $453.2 million and purchases of property and equipment of $410 thousand.

Previous wording

Net cash provided by financing activities for the six months ended June 30, 2024 of $16.0 thousand consisted of $257 thousand provided from the issuance of common stock under equity incentive plans off-set by cash used in the net-settlement of restricted stock unit vesting of $241 thousand.

Current wording

Net cash provided by financing activities for the nine months ended September 30, 2024 of $108.0 thousand consisted of $349 thousand provided from the issuance of common stock under equity incentive plans off-set by cash used in the net-settlement of restricted stock unit vesting of $241 thousand.

Previous wording

Net cash provided by financing activities for the six months ended June 30, 2023 of $237.0 million consists of $235.7 million provided from the issuance of common stock from underwritten offerings and $1.3 million provided from the issuance of common stock from equity incentive plans.

Current wording

Net cash provided by financing activities for the nine months ended September 30, 2023 of $237.3 million consists of $235.7 million provided from the issuance of common stock from underwritten offerings and $1.6 million provided from the issuance of common stock from equity incentive plans.

Previous wording

As of June 30, 2024, we have $2.7 million and $41.3 million in current and long-term lease liabilities, respectively. We believe that our existing cash, cash equivalents and marketable securities as of June 30, 2024 will be sufficient to fund our operating expenses and capital expenditure requirements into mid-2026. We have based these estimates on assumptions that may prove to be imprecise, and we could utilize our available capital resources sooner than we expect.

Current wording

As of September 30, 2024, we have $2.8 million and $40.5 million in current and long-term lease liabilities, respectively. We believe that our existing cash, cash equivalents and marketable securities as of September 30, 2024 will be sufficient to fund our operating expenses and capital expenditure requirements into mid-2026. We have based these estimates on assumptions that may prove to be imprecise, and we could utilize our available capital resources sooner than we expect.