NEXT Oncology

— Objective response rate (ORR) of 74% across all tested dose levels of ZL-1310 in patients with recurrent extensive-stage small cell lung cancer (SCLC) — Favorable pharmacokinetics (PK) and safety profile support continued evaluation of ZL-1310 as a single agent and in combination for the treatment of extensive-stage SCLC in recurrent and first-line therapy — Zai Lab to host conference call and webcast to discuss data on October 24, 2024, at 8:30 a.m. ET, following presentation of the data at ENA SHANGHAI, China & CAMBRIDGE, MA, USA I October 24, 2024 I Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today presented data from the ongoing global Phase 1a/1b study of ZL-1310, a potential best-in-class next-generation antibody-drug conjugate (ADC), at the EORTC-NCI-AACR (ENA) Symposium 2024 in Barcelona, Spain, as an oral presentation during the plenary session. ZL-1310 is being tested in patients with previously treated extensive-stage Small Cell Lung Cancer (ES-SCLC) after at least one prior platinum-based chemotherapy regimen. Data shared in the ENA presentation from the ongoing Part 1a monotherapy dose-escalation portion of the study included results from 25 patients across four dose cohorts (0.8 mg/kg, 1.6mg/kg, 2.0 mg/kg, and 2.4 mg/kg). Nineteen patients had evaluable tumor assessments. Key efficacy results include (n=19): Key safety findings include (n=25): All patients had progressed following standard platinum-based chemotherapy, and 92% of patients progressed after immune checkpoint inhibitors. Fifty-six percent had failed at least two prior lines of therapy. Twenty-eight percent of patients had brain metastases at baseline. At the time of the data cutoff, Oct. 10, 2024, 19 patients had at least one post-baseline tumor assessment per RECIST v1.1. DLL3 expression H-scores were assessed in 16 out of 19 patients. “The preliminary results from the ongoing Phase 1 trial of ZL-1310 suggest that this next-generation ADC therapy has the potential to deliver anti-tumor responses in the majority of patients with ES-SCLC, with good tolerability,” said Dr. Alex Spira, a medical oncologist at Virginia Cancer Specialists and NEXT Oncology. “This is particularly encouraging given the urgent need for improved treatment options for these patients. These promising data support continued evaluation of ZL-1310 as a monotherapy in the dose-expansion phase of the ongoing Phase 1 clinical trial and in combination.” “The ZL-1310 clinical program demonstrates Zai Lab’s commitment and ability to pursue novel modalities and validated cancer targets, and to advance innovative global oncology programs,” said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. “Based on the encouraging preliminary findings from our Phase 1 trial, we look forward to continuing development of ZL-1310 and advancing this promising asset across lines of therapy as part of our global oncology pipeline.” About Zai Lab Zai Lab (NASDAQ: ZLAB; HKEX: 9688; “Zai Lab”) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, immunology, neuroscience, and infectious disease. Our goal is to leverage our competencies and resources to positively impact human health in China and worldwide. For additional information about Zai Lab, please visit www.zailaboratory.com or follow us at www.twitter.com/ZaiLab_Global . About ZL-1310 ZL-1310 is a novel ADC in Zai Lab’s growing, global oncology pipeline that targets Delta-like ligand 3 (DLL3), an antigen that is overexpressed in many neuroendocrine tumors, is typically associated with poor clinical outcomes, and is a validated therapeutic target for SCLC. ZL-1310 comprises a humanized anti-DLL3 monoclonal antibody linked to a novel camptothecin derivative (a topoisomerase 1 inhibitor) as its payload. The compound was designed with a novel ADC technology platform called TMALIN ® , which leverages the tumor microenvironment to overcome challenges associated with first-generation ADC therapies, including off-target payload toxicity. The ongoing Phase 1a/1b clinical trial is evaluating ZL-1310 as monotherapy and in combination with atezolizumab, an immune checkpoint inhibitor, for the treatment of extensive-stage SCLC. SOURCE: Zai Lab

Phase 1 ACESOT-1051 clinical trial is evaluating APR-1051 as monotherapy treatment in patients with significant unmet medical need; active enrollment is ongoing at three sites in the U.S. Preliminary results to date demonstrate APR-1051 is safe and well-tolerated with no hematologic toxicity DOYLESTOWN, Pa., Oct. 23, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, today announced that preliminary safety results on its WEE1 inhibitor APR-1051 are highlighted in a poster being presented today at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, taking place in Barcelona, Spain. The results are from ACESOT-1051, a first-in-human Phase 1 study assessing the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. The dose escalation part of the study (Part 1) is currently ongoing and is expected to include up to 39 patients with advanced solid tumors. Oral APR-1051 is being administered once daily for 28-day cycles. A total of 8 cohorts are planned, evaluating doses of 10 mg to 150 mg once daily. So far, patients have been enrolled in single patient Cohorts 1, 2 and 3, evaluating subtherapeutic doses of 10 mg, 20 mg and 30 mg, respectively. Preliminary results Data are available on two of three patients, with a cutoff date of October 7, 2024 Preliminary results demonstrate that APR-1051 is safe and well-tolerated with no hematologic toxicityHemoglobin, hematocrit, and platelet counts were stable or increased slightly during the first treatment cycleThere were no signs of neutropenia, with white blood cells and neutrophils trending up for both patients during the first treatment cycleAll adverse events (AEs) recorded were Grade 1 and 2, with one Grade 1 AE (abdominal distention) possibly related to APR-1051No QT prolongation has been observedThree patients have been dosed to date with data available on two of these. One had disease progression at 49 days, a second withdrew following 36 days of treatment and dosing is ongoing in the third patient. “These preliminary data from our ongoing Phase 1 study are encouraging, showing that APR-1051 is safe and well-tolerated,” said Philippe Pultar, MD, Senior Medical Advisor and Lead of WEE1 Clinical Development at Aprea. “APR-1051 has been designed to be selective for WEE1, without the off-target inhibition of PLK or QT prolongation reported for other molecules in this class. We expect to confirm this favorable safety profile as we move to higher doses in the ACESOT-1051 trial. We are excited to explore the full therapeutic benefits of APR-1051, which has best in class potential, and hope to generate preliminary efficacy data from the study during 2025.” APR-1051 targets WEE1 kinase, an enzyme involved in the DNA damage response pathway. Based on preclinical studies, Aprea believes that APR-1051 may solve liabilities associated with other WEE1 inhibitors and is differentiated based on: 1) molecular structure; 2) selectivity for WEE1 versus off-target inhibition of the polo-like kinase, or PLK, family of kinases; 3) potentially improved pharmacokinetic (PK) properties; and 4) potential absence of QT prolongation at doses that significantly inhibit WEE1. No head-to-head studies with APR-1051 have been conducted. Active enrollment in ACESOT-1051 is ongoing at three sites in the U.S. (NEXT Oncology locations in San Antonio and Dallas, and The University of Texas MD Anderson Cancer Center) with planned additional sites. Anthony Tolcher M.D., Founder of Next Oncology commented, “The preliminary findings from ACESOT-1051 are promising and we are encouraged by the minimal toxicity in the patients treated so far. WEE1 kinase is a validated oncology target and represents an opportunity for therapeutic intervention in patients who otherwise have poor prognosis and no effective treatments today. We look forward to further exploring APR-1051's potential and are excited to recruit additional patients as the study progresses.” ACESOT-1051 Study Design ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) is a focused biomarker-driven study designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. Oral APR-1051 will be administered once daily for 28-day cycles. The study consists of two parts: Part 1 is dose escalation and is expected to enroll up to 39 patients with advanced solid tumors. The first three dose levels are using accelerated titration followed by Bayesian Optimal Interval (BOIN) design for the remaining dose levels; Part 2 (up to 40 patients) is designed for dose optimization, with the goal of selecting the Recommended Phase 2 Dose (RP2D). For more information, refer to Clinicaltrials.gov: NCT06260514. A copy of the poster will be available on Aprea’s corporate website today. Three additional posters will be available at the conclusion of the EORTC-NCI-AACR Symposium on Friday, October 25, 2024. About Aprea Aprea Therapeutics, Inc. is a clinical-stage biopharmaceutical company headquartered in Doylestown, Pennsylvania, focused on precision oncology through synthetic lethality. The Company’s lead program is ATRN-119, a clinical-stage small molecule ATR inhibitor in development for solid tumor indications. APR-1051, an oral, small molecule WEE1 inhibitor, recently entered the clinic. For more information, please visit the company website at www.aprea.com. The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Forward-Looking StatementCertain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended related to our study analyses, clinical trials, regulatory submissions, and projected cash position. We may, in some cases use terms such as “future,” “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team and on information currently available to management that involve risks, potential changes in circumstances, assumptions, and uncertainties. All statements contained in this press release other than statements of historical fact are forward-looking statements, including statements regarding our ability to develop, commercialize, and achieve market acceptance of our current and planned products and services, our research and development efforts, including timing considerations and other matters regarding our business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including, without limitation, risks related to the success, timing, and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected expenses), futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results (including, without limitation, any preclinical results or data), which are not necessarily indicative of the final results of our ongoing clinical trials, our understanding of product candidates mechanisms of action and interpretation of preclinical and early clinical results from its clinical development programs, and the other risks, uncertainties, and other factors described under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we file with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to update such forward-looking statements for any reason, except as required by law. Investor Contact:Mike MoyerLifeSci Advisorsmmoyer@lifesciadvisors.comMedia Contacts:Ignacio Guerrero-Ros, Ph.D., or David SchullRusso Partners, LLCIgnacio.guerrero-ros@russopartnersllc.comDavid.schull@russopartnersllc.com(858) 717-2310

Enrollment commenced in the ACESOT-1051 Phase 1 trial evaluating APR-1051 – no myelosuppression observed in the first of eight planned cohorts at sub-therapeutic dose $28.7 million in cash and cash equivalents as of June 30, 2024 with cash runway extended into Q4 2025 DOYLESTOWN, Pa., Aug. 12, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, today reported financial results for the second quarter ended June 30, 2024, and provided a business update. “Aprea continues to make excellent progress advancing its clinical pipeline of therapeutic candidates,” said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. “We initiated enrollment in the ACESOT-1051 trial, advancing a second clinical asset in our pipeline, APR-1051. APR-1051 is a next-generation inhibitor of WEE1 kinase which has been designed to limit toxicity. Based on its unique characteristics, we believe it could be best in class. We continue to enroll patients in the ABOYA-119 trial evaluating ATRN-119, our ATR inhibitor. We believe that our ongoing progress positions Aprea at the forefront of synthetic lethality drug development. We remain committed to developing new treatments that have a positive impact on the lives of cancer patients while creating value for our shareholders.” Key Business Updates and Potential Upcoming Key Milestones ACESOT-1051: A Biomarkers Focused, Phase 1 Trial of Oral WEE1 inhibitor, APR-1051, initiated APR-1051 is a potent and selective small molecule that has been designed to potentially solve liabilities and may achieve greater clinical activity than other WEE1 programs currently in development. Aprea is advancing APR-1051 as monotherapy in cancers with Cyclin E over expression, as well as other biomarkers that are predicted to be sensitive to WEE1 inhibition. Cancers overexpressing Cyclin E represent a high unmet medical need. Patients with Cyclin E overexpression have poor prognosis and, currently, have no effective therapies.In June 2024, enrollment commenced in the ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) Phase 1 clinical trial evaluating single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. The first patient was dosed at NEXT Oncology, San Antonio, Texas, without any dose-limiting toxicities (including myelosuppression) observed to date in the first cohort. A second patient has been enrolled at The University of Texas MD Anderson Cancer Center and has commenced treatment in the second dose cohort.The primary objectives of the Phase 1 study are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and recommended Phase 2 dose (RP2D); secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; pharmacodynamics is an exploratory objective.The Company will provide an update on the progress of this clinical study by year end. Open-label safety/efficacy data are expected in the first half of 2025.In June 2024, Aprea hosted a virtual KOL event to discuss APR-1051. Joseph Vacca, Ph.D., Medicinal Chemistry Expert and Consultant to Aprea, discussed the medicinal chemistry history, strategy-guided selective drug design, and preclinical findings of APR-1051. Eric J. Brown, Ph.D., University of Pennsylvania and Consultant to Aprea, discussed preclinical findings across the WEE1 inhibitor class. A replay of the event (with slides) can be accessed on Aprea’s corporate website here.APR-1051 was featured in two posters at the American Association of Cancer Research (AACR) annual meeting which took place in April 2024 in San Diego, which summarized the pre-clinical data supporting APR-1051 and the trial design for ACESOT-1051. ABOYA-119: Ongoing Clinical Trial Evaluating ATR inhibitor, ATRN-119 ATRN-119 is a potent and highly selective first-in-class macrocyclic ATR inhibitor, designed to be used in patients with mutations in DDR-related genes. Cancers with mutations in DDR-related genes represent a high unmet medical need. Patients with DDR-related gene mutations have a poor prognosis and, currently, have no effective therapies.ATRN-119 is currently being evaluated in the open-label Phase 1/2a clinical trial of ABOYA-119 (study AR-276-01) as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DDR-related genes. The first five dose cohorts (50mg to 550mg once daily) have been completed, and patients continue to enroll in additional cohorts in the dose escalation part of the trial.The primary endpoint of this Phase 1 trial is the tolerability and pharmacokinetics of ATRN-119 when administered orally on a continuous, once-daily schedule. Aprea is planning to amend the study protocol to add a group of patients who will receive ATRN-119 twice a day and to investigate the effect of food on ATRN-119 absorption and drug exposure in blood. Under the current protocol, the Company anticipates the ABOYA-119 Phase 1 readout to be available in the first half of 2025.An update on the ongoing trial was featured in a poster at the AACR Annual Meeting this past April. A copy of the AACR poster can be found here.For more information, please refer to clinicaltrials.gov NCT04905914. Corporate Appointed Nadeem Q. Mirza, M.D., M.P.H. as Chief Medical Officer (CMO), effective May 1, 2024. Dr. Mirza had been a consultant to Aprea since February 2023 and has now assumed a more central role in leading the Company's development of its expanding clinical pipeline. Select Financial Results for the Second Quarter ended June 30, 2024 As of June 30, 2024, the Company reported cash and cash equivalents of $28.7 million, compared to $21.6 million at December 31, 2023. The Company believes its cash and cash equivalents as of June 30, 2024, will be sufficient to meet its currently projected operating expenses and capital expenditure requirements into the fourth quarter of 2025.For the quarter ended June 30, 2024, the Company reported an operating loss of $3.8 million, compared to an operating loss of $3.7 million in the comparable period in 2023.Grant revenue, primarily from the National Cancer Institute of the National Institutes of Health (“NIH”) for the three months ended June 30, 2024, and 2023 was approximately $0.6 million and $0.2 million, respectively.Research and development expenses were approximately $2.6 million for the quarter ended June 30, 2024, compared to approximately $2.2 million for the comparable period in 2023. The increase was primarily due to an increase in expenses related to the initiation of ACESOT-1051, our Phase 1 dose-escalation study evaluating APR-1051, our small molecule WEE1 inhibitor, in the second quarter of 2024.General and administrative expenses were approximately $1.9 million for the quarter ended June 30, 2024, compared to approximately $1.7 million for the comparable period in 2023. The increase was primarily related to an increase in personnel costs primarily related to severance expense.The Company reported a net loss of $3.5 million ($0.58 per basic share) on approximately 5.9 million weighted-average common shares outstanding for the quarter ended June 30, 2024, compared to a net loss of $3.3 million ($0.87 per basic share) on approximately 3.7 million weighted average common shares outstanding for the comparable period in 2023. About Aprea Aprea Therapeutics, Inc. is a clinical-stage biopharmaceutical company headquartered in Doylestown, Pennsylvania, focused on precision oncology through synthetic lethality. The Company’s lead program is ATRN-119, a clinical-stage small molecule ATR inhibitor in development for solid tumor indications. APR-1051, an oral, small-molecule WEE1 inhibitor, recently entered the clinic. For more information, please visit the company website at www.aprea.com. The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Forward-Looking StatementCertain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended related to our study analyses, clinical trials, regulatory submissions, and projected cash position. We may, in some cases use terms such as “future,” “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team and on information currently available to management that involve risks, potential changes in circumstances, assumptions, and uncertainties. All statements contained in this press release other than statements of historical fact are forward-looking statements, including statements regarding our ability to develop, commercialize, and achieve market acceptance of our current and planned products and services, our research and development efforts, including timing considerations and other matters regarding our business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including, without limitation, risks related to the success, timing, and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected expenses), futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results (including, without limitation, any preclinical results or data), which are not necessarily indicative of the final results of our ongoing clinical trials, our understanding of product candidates mechanisms of action and interpretation of preclinical and early clinical results from its clinical development programs, and the other risks, uncertainties, and other factors described under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we file with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to update such forward-looking statements for any reason, except as required by law. Investor Contact: Mike MoyerLifeSci Advisorsmmoyer@lifesciadvisors.com Media Contact: Ignacio Guerrero-Ros, Ph.D., or David SchullRusso Partners, LLCIgnacio.guerrero-ros@russopartnersllc.comDavid.schull@russopartnersllc.com(858) 717-2310 Aprea Therapeutics, Inc.Consolidated Balance Sheets June 30, December 31, 2024 2023Assets Current assets: Cash and cash equivalents $28,694,694 $21,606,820 Prepaid expenses and other current assets 865,092 914,275 Total current assets 29,559,786 22,521,095 Property and equipment, net 92,379 88,362 Restricted cash 41,260 40,717 Other noncurrent assets 271,162 — Total assets $29,964,587 $22,650,174 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $964,327 $1,670,369 Accrued expenses 2,079,163 2,186,262 Deferred revenue 50,739 528,974 Total current liabilities 3,094,229 4,385,605 Total liabilities 3,094,229 4,385,605 Commitments and contingencies Series A convertible preferred stock, $0.001 par value, 40,000,000 shares authorized; 56,227 shares issued and outstanding at June 30, 2024 and December 31, 2023, respectively. 1,311,063 1,311,063 Stockholders’ equity: Common stock, $0.001 par value, 400,000,000 shares authorized, 5,430,215 and 3,736,673 shares issued and outstanding at June 30, 2024 and December 31, 2023, respectively. 5,430 3,736 Additional paid-in capital 350,566,533 335,644,204 Accumulated other comprehensive loss (10,649,364) (10,611,273)Accumulated deficit (314,363,304) (308,083,161)Total stockholders’ equity 25,559,295 16,953,506 Total liabilities and stockholders' equity $29,964,587 $22,650,174 Aprea Therapeutics, Inc.Consolidated Statements of Operations and Comprehensive Loss Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 (Unaudited) Grant revenue $561,574 $249,688 $942,143 $249,688 Operating expenses: Research and development 2,557,679 2,202,657 4,158,052 3,459,199 General and administrative 1,850,819 1,698,712 3,780,685 5,064,673 Total operating expenses 4,408,498 3,901,369 7,938,737 8,523,872 Loss from operations (3,846,924) (3,651,681) (6,996,594) (8,274,184)Other income (expense): Interest income, net 382,374 336,221 665,777 592,631 Foreign currency gain (loss) (5,502) 56,363 50,674 42,566 Total other income 376,872 392,584 716,451 635,197 Net loss $(3,470,052) $(3,259,097) $(6,280,143) $(7,638,987)Other comprehensive (loss) gain: Foreign currency translation (23,008) (73,420) (38,091) (11,464)Total comprehensive loss (3,493,060) (3,332,517) (6,318,234) (7,650,451)Net loss per share attributable to common stockholders, basic and diluted $(0.58) $(0.87) $(1.24) $(2.18)Weighted-average common shares outstanding, basic and diluted 5,937,291 3,731,571 5,067,809 3,497,329