hERG

DOYLESTOWN, Pa., Jan. 04, 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 provided a corporate update highlighting recent developments and plans for advancement of its pipeline of DNA Damage Response (DDR) anti-cancer agents in 2024. “Having made substantial progress over the past twelve months, we are well positioned for ongoing success in 2024 as we execute on our mission to be a global leader in synthetic lethality,” said Dr. Oren Gilad, President and CEO of Aprea. “We continue to advance towards achieving our milestones in the ongoing dose-escalation Phase 1 study of our novel macrocyclic ATR inhibitor, ATRN-119, and are finalizing submission of the IND for our next-generation, best-in-class WEE1 inhibitor, APR-1051. This IND is supported by a compelling pre-clinical package showing highly potent and selective anti-tumor activity, limited off-target effects, and favorable pharmacokinetics.” Update on Phase 1/2a Ongoing Trial of ATR Program, ATRN-119 Enrollment of patients continues in the dose escalation portion of the Phase 1/2a clinical trial (study AR-276-01) evaluating ATRN-119 in patients with advanced solid tumors having mutations in defined DDR-related genes. The primary objective of the Phase 1 part of this trial is evaluating the tolerability and pharmacokinetics of ATRN-119 when administered orally on a continuous, once-daily schedule. The daily dosing of ATRN-119 provides continuous ATR inhibition that may be preferable to intermittent dosing for both efficacy and safety, potentially supporting an important competitive advantage over the current class of ATR inhibitors. The secondary objective is the evaluation of antitumor efficacy. The most recent analysis of the data cut (January 2, 2024) shows that two patients have achieved stable disease – one each in the 50 mg and 200 mg cohorts. Importantly, both these patients’ tumors have mutations that have been predicted to confer sensitivity to ATR inhibition. The dose-limiting toxicity period for cohort 4 (350 mg) has been completed. The most recent patient with stable disease from cohort 3 (200mg), with a history of five prior lines of therapy is at approximately four months of treatment duration with ATRN-119, and, following clearance of the 350 mg cohort, is expected to be increased from 200 mg to 350 mg daily, as per the dose escalation trial protocol. ATRN-119 is being developed as the first and only macrocyclic ATR inhibitor. Macrocycles restrict the number of conformations that a molecule can form, potentially resulting in increased potency and increased selectivity. These properties are expected to permit higher dosing that is potentially more effective with increased tolerability and decreased off-target activity. The company plans to amend the design of the ongoing study beyond the current 800 mg high-dose cohort to incorporate additional higher dose groups. Upon the addition of the higher dose cohorts, Aprea expects to determine the recommended Phase 2 dose (RP2D) in the second half of 2024. Following dose escalation, the Phase 2a dose expansion part of the study may include patients with NSCLC, breast, colorectal, prostate, and ovarian cancers with selected genetic mutations. Importantly, the potential for reduced hematologic toxicity from ATRN-119 suggests it may be an ideal DDR inhibitor for novel combination therapies. These potential combinations include ATRN-119 with PARP inhibitors, WEE1 inhibitors, and Antibody-Drug Conjugates (ADCs). The latter of these possibilities could provide a significant breakthrough for the use of ADCs linked to standard chemotherapies, as these promising biopharmaceuticals are often constrained by aberrant drug release and dose-limiting toxicities. Combination with ATRN-119 would potentially amplify the DNA-damaging effects of these ADCs in the targeted tumor cells, thus affording greater efficacy at lower ADC doses. A more comprehensive dataset from the Phase 1 part of AR-276-01 will be submitted for presentation at a medical meeting in the first half of 2024. For more information, please refer to clinicaltrials.gov NCT04905914. Investigational New Drug (IND) for WEE1 Program, APR-1051 Aprea completed IND-enabling studies and is finalizing the submission of the IND application with the FDA to begin clinical trials of APR-1051 in the first half of the year. APR-1051 is being developed as a next-generation, potential best-in-class inhibitor of WEE1 kinase with the following properties: APR-1051 has a different molecular structure from all other WEE1 inhibitors currently in development with improved selectivity for the target. The improved properties of APR-1051 relative to the other WEE1 inhibitors include its limited effects on red blood cell counts, hERG inhibition, and body weight loss in pre-clinical studies. The selectivity of APR-1051 may solve a long-standing problem with WEE1 inhibitors. Preclinical studies have shown that APR-1051 is site-specific to WEE1 and does not significantly inhibit the PLK1, PLK2, and PLK3 family of kinases, potentially increasing the cancer-killing effects of WEE1i inhibition and reducing hematological toxicity caused by PLK off-targeting. PLK off-target activity has been a challenge for other WEE1 inhibitors. Recent studies indicate that PLK1 off-targeting partially counters the intracellular effects of WEE1 inhibition and could potentially contribute to the myelosuppression observed with other WEE1 inhibitors.Specific genetic mutations driving patient selection have been identified. The company expects to receive FDA clearance on the IND during Q1 2024. Clinical development is in line with FDA requirements for a dose escalation trial to evaluate safety and pharmacokinetics. Leading institutions and a Principal Investigator have been identified for the trial. Company to Participate in 2024 Corporate Access Event Aprea will be hosting institutional investor and business development meetings at the Annual Corporate Access Event in San Francisco, hosted by our investor relations firm LifeSci Partners. Management will be available for meetings on Wednesday, January 10, 2024. To schedule a meeting, interested parties can register here or send an email to access@lifesciadvisors.com. About ApreaAprea 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. Aprea completed all IND enabling studies and is moving towards the submission of an oral, small molecule WEE1 inhibitor, APR-1051. 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 Statement Certain 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, 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, 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

DOYLESTOWN, Pa., Nov. 09, 2023 (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 three and nine months ended September 30, 2023, and provided a business update. “We are very pleased by the progress of our diversified programs this past quarter. Importantly, we presented initial clinical data from our Phase 1/2a study of our ATR inhibitor, ATRN-119, in solid tumors in a poster at the recent AACR-NCI-EORTC International Conference. To date, ATRN-119 has demonstrated an ability to be a very compelling molecule, appearing to be well tolerated with no reports of dose-limiting toxicities and ongoing daily dosing may result in persistent tumor-reducing effect,” said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. “We are continuing with patients in the dose escalation portion of the study, and the dose expansion cohort is on track to be initiated in 2Q 2024. In our WEE1 inhibitor, ATRN-1051, program we are on track to file an IND with the FDA by the end of 2023, and plan to begin clinical testing in the first half of 2024. Our strong balance sheet continues to support our strategy and plans through our near-term milestones in both our ATR and WEE1 programs, with a cash runway through the end of the fourth quarter of 2024. We look forward to providing more updates as we make progress and reach important milestones in the coming weeks and months.” Key Business and Financial Updates Hosted a Key Opinion Leader (KOL) event on October 31, 2023, highlighting the Company’s portfolio of small molecules focused on Synthetic Lethality (SL) by targeting the DNA Damage Response (DDR) Pathways. The event featured Key Opinion Leaders Dr. Fiona Simpkins, Professor in the Division of Gynecology Oncology and Department of OB-GYN at the University of Pennsylvania, Dr. Timothy Yap, medical oncology physician-scientist and Professor at the University of Texas MD Anderson Cancer Center, Dr. Eric Brown, a consultant to Aprea and a Professor at the University of Pennsylvania and a member of the Abramson Family Cancer Research Institute, and Aprea’s Dr. Nadeem Mirza, Senior Medical Advisor. The speakers, along with the management team, provided an overview of the Company’s lead ATR inhibitor candidate, ATRN-119, and its WEE1 inhibitor candidate, ATRN-1051, and highlighted the addressable unmet clinical need and potential combination therapies using these programs.Presented initial clinical data on the Company’s ATR inhibitor, ATRN-119, and preclinical data on its WEE1 inhibitor, ATRN-1051, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on October 14, 2023. The first poster included initial data from the Company’s first-in-human Phase 1/2a dose escalation trial of ATRN-119 in solid tumors. The trial is being conducted to determine the recommended Phase 2 dose, with a daily dosing administration over a 56-day cycle. The Company is actively enrolling cohort 4 at 350mg, with subsequent 550mg cohort 5 and 800mg cohort 6 planned. The Company anticipates enrolling the first patient in the dose expansion portion of the study in Q2 2024.The second poster presented preclinical data from the Company’s WEE1 inhibitor program that demonstrated the potential safety and efficacy of its highly differentiated WEE1 inhibitor, ATRN-1051, in the treatment of ovarian cancer. The data showed ATRN-1051 to be a highly potent and selective inhibitor of WEE1 that does not significantly affect the off-target PLK1, PLK2, and PLK3 family of kinases. ATRN-1051 shows potentially favorable PK properties and appears to cause lower inhibition of hERG, a potential indication of low cardiotoxicity. Importantly, at doses and scheduling that suppress tumor growth, ATRN-1051 causes little anemia. These findings have justified IND-enabling studies for clinical development of ATRN-1051. Evidence generated by Aprea suggests such off-targeting of the PLK family, which has been a challenge for other WEE1 inhibitors in the class, substantially limits the ability of WEE1 inhibitors to cause cell death.Appointed Dr. Jean-Pierre Bizzari to its Board of Directors. Dr. Bizzari has been responsible for numerous global approvals of several billion-dollar therapies, has been involved in acquisition and licensing agreements with several major pharmaceutical companies, and is a member and leader on many scientific committees. The Company also named Dr. Richard Peters as Chairman of the Board; Dr. Peters has served as a member of the Board since June 2020 bringing over 2 decades of experience in developing new therapies for difficult-to-treat diseases. Potential Upcoming Key Milestones ATR Inhibitor Clinical Program (ATRN-119) Phase 1/2a Monotherapy Dose Escalation study 1Q 2024 Complete dose escalation Phase 1/2a Monotherapy Dose Expansion study 2Q 2024 First patient enrolled WEE1 Inhibitor Program (ATRN-1051) IND 4Q 2023 IND Submission1Q 2024 IND Clearance Phase 1/2a Monotherapy Dose Escalation Study 1H 2024 First patient enrolled Select Financial Results for the Third Quarter ended September 30, 2023 As of September 30, 2023, the Company reported cash and cash equivalents of $25.4 million.For the quarter ended September 30, 2023, the Company reported an operating loss of $3.5 million, compared to an operating loss of $4.2 million for the same period in 2022.Research and Development (R&D) expenses were $2.1 million for the quarter ended September 30, 2023, compared to $1.1 million for the same period in 2022. The increase in R&D expense was related to IND enabling studies for ATRN-1051, the Company’s small molecule WEE1 inhibitor, offset in part by a decrease in personnel costs related to the former facility in Sweden.General and Administrative (G&A) expenses were $1.7 million for the quarter ended September 30, 2023, compared to $3.1 million for the same period in 2022. The decrease in G&A expenses was due to a decrease in professional fees primarily associated with post-acquisition activities during 2022, a decrease in insurance premiums, and a decrease in personnel costs related to the former facility in Sweden.The Company reported a net loss of $3.2 million ($0.86 per basic share) on approximately 3.7 million weighted-average common shares outstanding for the quarter ended September 30, 2023, compared to a net loss of $4.0 million ($2.32 per basic share) on approximately 1.7 million weighted average common shares outstanding for the same period in 2022. About ApreaAprea 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. Its oral, small molecule WEE1 inhibitor, ATRN-1051, is being advanced to IND submission. 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 Statement Certain 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, 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, 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 +++ Tables to Follow +++ Aprea Therapeutics, Inc. Condensed Consolidated Balance Sheets (Unaudited) September 30, December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $25,353,513 $28,786,647 Prepaid expenses and other current assets 286,263 1,366,859 Total current assets 25,639,776 30,153,506 Property and equipment, net 86,198 2,321 Restricted cash 40,449 — Total assets $25,766,423 $30,155,827 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $862,552 $842,754 Accrued expenses 3,303,510 2,358,332 Total current liabilities 4,166,062 3,201,086 Commitments and contingencies Series A convertible preferred stock, $0.001 par value, 40,000,000 shares authorized; 56,227 shares issued and outstanding at September 30, 2023 and December 31, 2022, respectively. 1,311,063 1,311,063 Stockholders’ equity: Common stock, $0.001 par value, 400,000,000 shares authorized, 3,736,673 and 2,655,269 shares issued and outstanding at September 30, 2023 and December 31, 2022, respectively. 3,736 2,655 Additional paid-in capital 335,561,343 330,060,836 Accumulated other comprehensive loss (10,635,874) (10,623,408) Accumulated deficit (304,639,907) (293,796,405) Total stockholders’ equity 20,289,298 25,643,678 Total liabilities and stockholders' equity $25,766,423 $30,155,827 Aprea Therapeutics, Inc. Condensed Consolidated Statements of Operations and Comprehensive Loss (Unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Grant revenue $319,468 $— $569,156 $— Operating expenses: Research and development 2,122,603 1,117,576 5,581,802 15,870,867 General and administrative 1,719,715 3,082,618 6,784,388 18,849,549 Acquired in-process research and development — — — 76,020,184 Total operating expenses 3,842,318 4,200,194 12,366,190 110,740,600 Loss from operations (3,522,850) (4,200,194) (11,797,034) (110,740,600) Other income: Interest income, net 321,215 151,123 913,846 205,585 Foreign currency gain (2,880) 24,353 39,686 315,130 Total other income 318,335 175,476 953,532 520,715 Net loss $(3,204,515) $(4,024,718) $(10,843,502) $(110,219,885) Other comprehensive loss: Foreign currency translation (1,002) 26,161 (12,466) 118,311 Total comprehensive loss (3,205,517) (3,998,557) (10,855,968) (110,101,574) Net loss per share attributable to common stockholders, basic and diluted $(0.86) $(2.32) $(3.03) $(83.33) Weighted-average common shares outstanding, basic and diluted 3,735,176 1,732,783 3,577,482 1,322,652

Pictured: Pills organized in a digital pattern/iStock, EvilWata When Alex Zhavoronkov launched Insilico Medicine in 2014, the company’s main focus was on using artificial intelligence as an alternative to animal testing for pharmaceutical research and development. Using deep learning, an advanced form of machine learning, the company aimed to predict how drug compounds would affect cells and what the side effects might be. Fast forward to 2023, and Insilico has evolved into an end-to-end AI-driven biotech company, deploying AI from lead and target discovery through clinical trials. Insilico’s Pharma.AI platform, backed by $2 trillion in machine-readable research data, contains over 40 generative algorithms. The firm uncovered the intracellular “Target X” for idiopathic pulmonary fibrosis (IPF) using AI analysis, and subsequently developed a novel small molecule inhibitor, INS018_055, which has shown potential in preclinical studies for improved fibrotic disease treatment with fewer side effects. In August, it became the first drug fully generated by AI to enter a Phase II trial. Making up the Pharma.AI platform, Insilico’s PandaOmics for target discovery, Chemistry42 for drug design and InClinico for clinical trial prediction “work together in an end-to-end feedback loop,” Zhavoronkov explained. “However, safety of the target is accounted for at two different stages,” said Alex Aliper, president of Insilico. First, PandaOmics uses relevant existing information to find the safest and most promising therapeutic targets, while Chemsitry42 enables multi-parametric optimization of the molecules. The latter includes ADMET predictors, a machine learning (ML) software tool, to assess how the body processes the generated molecule, covering aspects like absorption, distribution, metabolism, elimination and toxicity, as well as enzyme inhibition like cytochrome P450, which is involved in drug side effects. “Chemistry42 also has around 500 medicinal chemistry filters that filter out compounds with structural motifs known to be toxic,” Aliper told BioSpace. “Our initial studies have indicated that INS018_055 has the potential to address some of the limitations of current IPF therapies—including unpleasant side effects—and we are hopeful that the data from our current and future clinical trials will confirm this belief,” Zhavoronkov said. Schrödinger’s Selectivity New York- and Germany–based Schrödinger focuses on the safety of small-molecule drugs. Its platform blends AI/ML efficiency with physics-based accuracy, enabling its specialists to design and synthesize desired molecules, thus reducing time and costs. “In some cases, the clinical candidate has been selected after synthesizing just 100 molecules instead of the thousands made using traditional design approaches,” said Robert Abel, the company’s chief computational scientist. In order to minimize drug side effects, Schrödinger uses its platform to design molecules that bind potently and selectively to the intended protein target versus related proteins, explained Karen Akinsanya, president of R&D, therapeutics at Schrödinger. “This approach allows us to find molecules that might provide a therapeutic benefit without binding to hERG, CYPs, PXR and other well-known off-target proteins that are well known to cause side effects,” she told BioSpace. The hERG gene is crucial for heart rhythm regulation; CYPs, or cytochromes, are liver enzymes that metabolize drugs, potentially causing interactions; PXR, a cellular protein, helps process drugs and foreign substances by influencing enzyme production. These factors are vital in drug development and medication safety, Akinsanya said. “Protein structures, including binding sites, are crucial for our computational platform, but starting a drug discovery project often lacks enough experimental data for naive AI approaches due to the vast chemical space, which exceeds available data,” she explained. “Schrödinger addresses this by using advanced physics-based calculations to efficiently generate the needed binding affinity datasets.” Both Insilico and Schrödinger use AI to discover drugs that they claim would be safer than those hunted down using non-AI methods. Big pharma players also entered this space a few years ago, either directly or by partnering with tech companies or incubating smaller AI-based startups. AstraZeneca collaborated with BenevolentAI to discover new targets and predict potential drug side effects by analyzing scientific literature, clinical trial data and biomedical databases. Novartis employs AI for intelligent molecular design to develop safe molecules for patients. By analyzing various data sources, including chemical properties and biological interactions, the company aims to identify compounds with lower risk pro Meanwhile, Merck KGaA has been busy inking AI deals aimed at making safer medicines. In 2018, Merck struck an alliance with Canadian company Cyclica that uses the latter’s cloud-based technology to uncover new drug targets and identify off-target adverse effects. Then, in February 2022, the company announced a partnership to leverage Quris’ BioAI safety prediction platform, which uses miniaturized human tissues on a chip, nano-sensing and machine learning to predict the safety of drug candidates in humans. Confidence and Caution AI’s potential in drug development is often recognized with respect to saving time and money. However, its increasing deployment in drug safety studies elicits both confidence and caution from industry and researchers, according to experts such as Andreas Bender, a chemoinformatics researcher at the University of Cambridge, U.K. Bender, who has been working with AstraZeneca on computational drug safety studies, said there is often a “tech push and a science pull” about AI. Although data collection becomes easier, understanding the data’s signal is more critical, he told BioSpace. “We have quite a lot of data, but we don’t understand much of that pile, like how certain biological mechanisms relate to a phenotype,” he said. Using AI to identify potential side effects is “like [finding] a needle in a haystack.” Drug safety lies not just in how the molecule has been designed but also in other factors. For example, Bender explained, the use of excipients—the inert or slightly active substances used in formulating a drug compound into a drug product—and other additives can affect a drug’s safety profile, as can patient biology and environmental stimuli. “There are mechanistic side effects that you know where they come from and what to do about, but there are also idiosyncratic side effects that you don’t know where they come from, so you cannot predict such adverse reactions using AI,” he said. Hence, along with machine learning, his group’s research also integrates chemical biology and human physiology to predict drug toxicity. There are multiple other challenges, Bender continued, such as how different countries define specific side effects. “How do we translate, then, the [computational predictions] into decision-making?” he asked. “That integration is often where the real problems come from, and that’s why you always need to integrate computers with experiments—[to] follow up on predictions.” Still, he said, AI-based predictions of drug safety could improve the drug development process. “It is, rather, about making better decisions. I’m not saying nothing works, but also not that everything works; just . . . that finding meaningful signals in drug safety prediction is statistically more difficult and depends on several [kinds of] data, so promises must be cautious and realistic.” Vijay Shankar Balakrishnan is a freelance journalist based in Ludwigshafen, Germany. Reach him at LinkedIn.