PARP1 inhibitors(Poly (ADP-Ribose) polymerase 1 inhibitors), PARP2 inhibitors(Poly (ADP-Ribose) Polymerase 2 inhibitors), PARP3 inhibitors(Poly (ADP-Ribose) Polymerase 3 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [10]

Active Indication

Advanced Endometrial CarcinomaRecurrent Endometrial CancerBRCA mutation positive Breast Cancer+ [134]

Inactive Indication

Adenocarcinoma of EsophagusAdvanced Cervical CarcinomaAdvanced Lung Non-Small Cell Carcinoma+ [31]

Originator Organization

AstraZeneca PLC

Active Organization

Novartis Pharmaceuticals Corp.

AstraZeneca PLCMerck Sharp & Dohme LLC

+ [14]

Inactive Organization

Syndax Pharmaceuticals, Inc.

Sandoz International GmbH

Novartis AG

License Organization

Merck & Co., Inc.

AstraZeneca PLC

Breast International Group

+ [1]

Drug Highest PhaseApproved

First Approval Date

European Union (16 Dec 2014),

BRCA Mutation Castration-Resistant Prostate CancerBRCA-mutated Fallopian Tube CarcinomaBRCA-mutated Ovarian Cancer+ [12]

RegulationBreakthrough Therapy (United States), Fast Track (United States), Accelerated Approval (United States), Orphan Drug (United States), Priority Review (China), Conditional marketing approval (China), Special Review Project (China), Orphan Drug (Japan), Priority Review (Australia), Accelerated Approval (Canada), Priority Review (United States)

Structure/Sequence

Molecular FormulaC24H23FN4O3

InChIKeyFDLYAMZZIXQODN-UHFFFAOYSA-N

CAS Registry763113-22-0

508

Clinical Trials associated with Olaparib

NCT06856499

/ Not yet recruitingPhase 1IIT

Phase I Evaluation of Combination CLK/DYRK (Cirtuvivint) Inhibition with PARP Inhibition (Olaparib) in BRCA/HRD Platinum Resistant Ovarian Cancer

The purpose of this study is to learn about the safety and tolerability of Cirtuvivint in combination with Olaparib in platinum resistant ovarian cancer. The study also aims to determine the recommended dose of the combination therapy.
If a participant is a good fit for the study, and they enroll in the study, they will:
* Visit the clinic often at the beginning of the study for physical exams, blood draws, vital signs, and other study and routine care procedures. After the first two months participants will visit the clinic every 28 days.
* Take the study medications, Cirtuvivint and Olaparib. Participants will take Olaparib every day. Participants will either take Cirtuvivint 5 days per week or 2 days per week.

Start Date01 Dec 2025

Sponsor / Collaborator

University of Colorado Denver

[+2]

NCT05128734

/ Not yet recruitingPhase 2IIT

A Randomized Phase II Study of Temozolomide Monotherapy or in Combination With Olaparib in Patients With METHYLATED 06-Methylguanine-DNA Methyltransferase (MGMT) Pre-Treated Triple Negative Breast Cancer (TNBC)

This is a randomized phase II study to evaluate the disease control rate (DCR) of patients with metastatic or locally advanced METHYLATED 06-methylguanine-DNA methyltransferase (MGMT) with triple-negative breast cancer (TNBC) treated with Temozolomide ± Olaparib. Patients will be randomized 1:1 to Treatment Arm 1 (temozolomide treatment) or Arm 2 (temozolomide plus olaparib treatment).

Start Date01 Sep 2025

Sponsor / Collaborator

AHS Cancer Control Alberta

NCT06915025

/ Not yet recruitingPhase 3

A Randomized Phase 3 Trial Evaluating the Safety & Efficacy of IP IMNN-001 Administered in Combination w/ Standard Neoadjuvant & Adjuvant Chemotherapy in Newly Diagnosed Patients w/ Advanced EOC, Fallopian Tube or Primary Peritoneal Cancer

This is a randomized, adaptive, open label, multicenter trial to evaluate the safety and efficacy of intraperitoneal (IP) IMNN-001 plus chemotherapy compared to chemotherapy alone.

Start Date21 Apr 2025

Sponsor / Collaborator

Imunon, Inc.

100 Clinical Results associated with Olaparib

100 Translational Medicine associated with Olaparib

100 Patents (Medical) associated with Olaparib

4,733

Literatures (Medical) associated with Olaparib

31 Dec 2025·INTERNATIONAL JOURNAL OF HYPERTHERMIA

Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model

Article

Author: van Bochove, Gregor G. W. ; Rodermond, Hans M. ; Oei, Arlene L. ; Krawczyk, Przemek M. ; Stalpers, Lukas J. A. ; Franken, Nicolaas A. P. ; Scutigliani, Enzo M. ; Mei, Xionge ; Crezee, Johannes ; IJff, Marloes

Background: Efficacy of current treatment options for cervical cancer require improvement. Previous in vitro studies have shown the enhancing effects of the addition of PARP1-inhibitors to chemoradiotherapy and thermoradiotherapy. The aim of our present study was to test efficacy of different combinations of treatment modalities radiotherapy, cisplatin, hyperthermia and PARP1-inhibitors using in vitro tumor models, ex vivo treated patient samples and in vivo tumor models.Materials and Methods: In vitro clonogenic survival curves (0-6 Gy) show that PARP1-i (4-5 M Olaparib) enhances both chemoradiotherapy (0.3-0.5 µM cisplatin) and thermoradiotherapy (42 °C for 1 h) in SiHa, CaSki and HeLa cells. A cervical cancer mouse model and freshly obtained in-house developed patient-derived organoids were used to examine the effects of different treatment combinations. For the in vivo study, human cervical cancer (SiHa) cells were injected in the right hind leg of athymic nude mice. In vivo mouse experiments show that PARP1-i enhances thermoradiotherapy or chemoradiotherapy by reduction of tumor volumes. Five cycles of treatment were applied with the following doses per cycle: irradiation 3 Gy, hyperthermia 1 h at 42 °C, cisplatin at 2 mg/kg, and twice PARP1-i at 50 mg/kg.Results: Quadruple treatment, combining radiotherapy, hyperthermia, cisplatin and PARP1-i, was very effective but also lead to severe side effects causing severe weight loss and death. In contrast, thermoradiotherapy or chemoradiotherapy with addition of PARP1-i, were effective without serious side effects.Conclusion: The triple combinations are promising options for potentially more effective treatment of locally advanced cervical cancer without more toxicity.

31 Dec 2025·ANNALS OF MEDICINE

Haematologic outcomes and associated clinical characteristics among patients receiving Olaparib therapy in the UAE: a retrospective chart review

Article

Author: Akour, Amal ; Nabil, Said ; Ibrahim, Mariam ; Kendakji, Saba ; ZainAlAbdin, Sham ; Aburuz, Salahdein ; Wahba, Lina

BACKGROUND:

Poly ADP ribose polymerase (PARP) inhibitors, such as Olaparib (Lynparza^®), are pivotal in treating certain cancers, particularly those linked to BReast CAncer gene (BRCA) mutations. Despite its established efficacy, Olaparib use is associated with various adverse events (AEs), notably haematologic toxicities, such as anaemia. This retrospective chart review study aimed to examine haematologic outcomes and associated factors in patients treated with Olaparib at a tertiary hospital in the UAE.

METHODS:

We reviewed the medical charts of patients prescribed Olaparib and focused on haematologic indices at a baseline of 1-month, 3-month and 6-month follow-up periods. Data were analysed to determine the AEs frequency, transfusions need and potential associated patients' clinical characteristics.

RESULTS:

This study included all patients who received Olaparib (n = 66). Most patients were females (n = 61; 92.4%) and the vast majority were non-smokers (97%) and free of hepatic disease. Themean age of the patients was 57.03-year-old (SD) = 12.06 years), and body mass index (BMI) was 28.16 (SD = 6.40) kg/m². A high rate of anaemia (70.8%) was detected among the patients during their Olaparib therapy. Approximately, one-third of the patients developed neutropenia and thrombocytopenia. Transfusion was needed in almost half of the patients. Glomerular filtration rate (GFR) and neutropenia were significantly correlated with moderate-severe anaemia (OR = 0.097, 95% CI: 0.011-0.88, p value = .038) and (OR = 9.04, 95% CI: 1.024-79.78, p value = .048), respectively.

CONCLUSIONS:

Our findings highlight the side effects of Olaparib therapy in terms of haematology which could be avoided. Further studies are needed to better understand the therapeutic management of Olaparib and the mitigation of haematologic complications.

01 Oct 2025·COMPUTATIONAL BIOLOGY AND CHEMISTRY

The drug discovery candidate for targeting PARP1 with Onosma. Dichroantha compounds in triple-negative breast cancer: A virtual screening and molecular dynamic simulation

Article

Author: Mishra, Anurag ; Chandra, Muktesh ; Hamad, Atheer Khdyair ; Jawad, Mahmood Jasem ; Taher, Waam Mohammed ; Kareem, Radhwan Abdul ; Verma, Lokesh ; Prasad, G V Siva ; Alwan, Mariem ; Ahmed, Hanan Hassan ; Saadh, Mohamed J

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the overexpression of poly-ADP ribose polymerase 1 (PARP1), a key enzyme in DNA repair. Targeting PARP1 with inhibitors presents a promising therapeutic strategy, particularly given the limited treatment options for TNBC. This study employed in silico methodologies to evaluate the pharmacokinetic and inhibitory potential of FDA-approved drugs and compounds derived from Onosma. dichroantha root extracts against PARP1. Virtual screening and molecular docking identified Midazolam, Olaparib, Beta-sitosterol, and 1-Hexyl-4-nitrobenzene as top candidates, exhibiting strong binding affinities of -10.6 kcal/mol, -9.9 kcal/mol, -6.83 kcal/mol, and -5.53 kcal/mol respectively. Molecular dynamics simulations (MDS) over 100 nanoseconds revealed that Beta-sitosterol formed the most stable complex with PARP1, demonstrating minimal structural deviations and robust hydrogen bonding. The Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) analysis further confirmed Beta-Sitosterol and Olaparib superior binding free energy (ΔG_bind= -175.43 kcal/mol and -180.8 kcal/mol respectively), highlighting its potential as a potent PARP1 inhibitor. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling indicated that Beta-Sitosterol adheres to Lipinski's Rule of Five, with high intestinal absorption (95.88 %) and blood-brain barrier permeability (0.824), despite low water solubility. Protein-protein interaction analysis identified key PARP1-associated proteins, including CASP3, CASP7, and XRCC1, suggesting broader therapeutic implications. These findings underscore the potential of Beta-Sitosterol as a novel PARP1 inhibitor for TNBC treatment, combining computational validation with favorable pharmacokinetic properties. The study also highlights the utility of drug repurposing and plant-derived compounds in developing targeted therapies for TNBC, paving the way for further preclinical and clinical investigations.

629

News (Medical) associated with Olaparib

07 May 2025

·www.astrazeneca.com

Enhertu followed by THP before surgery showed statistically significant and clinically meaningful improvement in pathologic complete response in patients with high-risk HER2-positive early-stage breast cancer in DESTINY-Breast11 Phase III trial

Positive high-level results from the DESTINY-Breast11 Phase III trial showed Enhertu (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab and pertuzumab (THP) demonstrated a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) rate versus standard of care (dose-dense doxorubicin and cyclophosphamide followed by THP [ddAC-THP]) when used in the neoadjuvant setting (before surgery) in patients with high-risk, locally advanced HER2-positive early-stage breast cancer. Pathologic complete response is defined as no evidence of invasive cancer cells in the removed breast tissue and lymph nodes following treatment. The secondary endpoint of event-free survival (EFS) was not mature at the time of analysis; however, EFS data showed an early positive trend favouring Enhertu followed by THP compared to standard of care. The trial will continue to follow EFS. Approximately one in three patients with early-stage breast cancer are considered high risk, as they are more likely to experience disease recurrence and have a poor prognosis.1,2 Achieving pCR in early-stage HER2-positive breast cancer is associated with improved long-term outcomes.2,3 The current standard of care in many regions of the world in this neoadjuvant setting involves combination chemotherapy regimens.2 These regimens often include anthracyclines, which can be challenging for patients to tolerate and may result in long-term cardiovascular side effects.4 Further, nearly half of patients who receive neoadjuvant treatment do not achieve pCR, reinforcing the need for new treatment options.2,3 Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “The clinically meaningful improvement in pathologic complete response and the safety data seen in DESTINY-Breast11 highlight the potential of Enhertu to challenge the current standard of care in early-stage HER2-positive breast cancer. Enhertu is already an important treatment option in the metastatic setting, and these data have the potential to allow this medicine to move into early stages of disease where cure is possible.” Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “There are still many patients with early-stage breast cancer who do not achieve a pathologic complete response with treatment in the neoadjuvant setting, increasing the risk of disease recurrence. These topline results from DESTINY-Breast11 demonstrate that Enhertu followed by THP could offer patients with HER2-positive breast cancer a promising new treatment approach prior to surgery, setting more patients on a path towards a potential cure." Enhertu followed by THP showed an improved safety profile compared to ddAC-THP. The safety profiles of Enhertu and THP were consistent with the known profiles of each individual medicine with no new safety concerns identified. Rates of interstitial lung disease were similar across the Enhertu followed by THP and the ddAC-THP arms as determined by an independent adjudication committee. Following a recommendation by the Independent Data Monitoring Committee, patient enrolment in a third arm of the trial evaluating Enhertu alone was closed after a previous interim efficacy assessment of the trial arms. Data from DESTINY-Breast11 will be presented at an upcoming medical meeting and shared with regulatory authorities. Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. Enhertu has demonstrated improved outcomes in six Phase III breast cancer trials across different subtypes and stages of disease, including the recently announced DESTINY-Breast09 Phase III trial in the 1st-line HER2-positive metastatic setting. Enhertu is also being studied in several ongoing breast cancer trials including the DESTINY-Breast05 Phase III trial which is evaluating Enhertu in the high-risk adjuvant early HER2-positive setting. Notes HER2-positive early breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.5 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.5 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.6 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.7 Approximately one in five cases of breast cancer are considered HER2-positive.8 DESTINY-Breast11 DESTINY-Breast11 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of neoadjuvant Enhertu (5.4mg/kg) monotherapy or Enhertu followed by THP vs. the standard of care regimen in patients with high-risk (lymph node positive [N1-3] or primary tumour stage T3-4), locally advanced or inflammatory HER2-positive early-stage breast cancer. Patients were randomised 1:1:1 to receive either eight cycles of Enhertu monotherapy; four cycles of Enhertu followed by four cycles of THP; or four cycles of ddAC (dose-dense doxorubicin and cyclophosphamide) followed by four cycles of THP. The primary endpoint of DESTINY-Breast11 is pCR (absence of invasive disease in the breast and lymph nodes). Secondary endpoints include EFS, invasive disease-free survival, overall survival and safety. DESTINY-Breast11 enrolled 927 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov. Enhertu Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. Enhertu (5.4mg/kg) is approved in more than 50 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (6.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication will depend on whether a randomised controlled confirmatory clinical trial can demonstrate clinical benefit in this population. Enhertu (5.4mg/kg) is approved in the US and other countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the US is contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu development programme A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2-targetable cancers. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway (datopotamab deruxtecan), and next-generation oral SERD and potential new medicine camizestrant. PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab). AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References Matthew Bowden Company Secretary AstraZeneca PLC Oncology Corporate and financial

Clinical ResultPhase 3Drug ApprovalImmunotherapyLicense out/in

05 May 2025

·www.businesswire.com

Lantern Advances Drug Candidate LP-184 with IND Clearance for Phase 1b/2 Clinical Trial in Triple Negative Breast Cancer (TNBC)

DALLAS--(BUSINESS WIRE)--Lantern Pharma Inc. (Nasdaq: LTRN), an artificial intelligence company developing targeted and transformative cancer therapies using its proprietary AI platform, RADR®, today announced that it has received clearance of its Investigational New Drug Application (IND) from the U.S. Food and Drug Administration (FDA) for a Phase 1b/2 clinical trial for LP-184 in Triple Negative Breast Cancer. This achievement builds on the previous regulatory momentum including Orphan Drug Designation in 2023 and Fast Track Designation in 20241. "This IND clearance for LP-184 in a Phase 1b/2 study represents a pivotal advancement in our mission to bring precisely targeted, AI-developed medicines to patients with aggressive cancers and limited treatment options," said Panna Sharma, CEO & President. Strategic Trial Design to Address Critical Treatment Gap in TNBC The innovative dual-approach in the clinical trial is designed to evaluate LP-184 in recurrent, advanced-stage TNBC patients through: Monotherapy Arm: An open-label study involving approximately 30 patients with advanced-stage TNBC, focusing on dose optimization to evaluate, enhance and optimize safety and potential efficacy for TNBC patients. Combination Therapy: Evaluation of LP-184 in combination with olaparib in second-line settings for patients with advanced-stage TNBC harboring BRCA1 or BRCA2 alterations, with primary endpoints including safety and efficacy parameters that could potentially support a pathway to regulatory approval. This strategic approach focuses on addressing a significant unmet medical need, with average survival for newly diagnosed metastatic TNBC estimated at 10 to 18 months, representing an annual market opportunity exceeding $4 billion USD. LP-184 Background in TNBC & Mechanistic Rationale LP-184 is a synthetically lethal small molecule that induces DNA double strand breaks upon bioactivation by the enzyme prostaglandin reductase 1 (PTGR1) in cancer cells. Preclinical studies and artificial intelligence-driven in silico modeling suggest that cancers with DDR gene alterations may preferentially respond to LP-184.2 Preclinical findings also suggest that LP-184 is particularly well positioned for TNBC with striking data from in vivo models including complete regression seen in several PARP resistant as well as PARP sensitive PDXs (see Figure 1). Nearly 70% of TNBCs are noted to harbor deficiency in homologous recombination pathways, making them likely to be particularly sensitive tumors for targeting with drug-candidate LP-184. In addition, it is estimated that up to 46% percent of women with TNBC will develop brain metastasis3, and LP-184 has shown blood brain barrier (BBB) penetration, with evidence of activity in preclinical brain metastasis models. LP-184 Phase 1b/2 TNBC Trial Overview - Monotherapy The monotherapy phase 1b/2 trial is designed to evaluate LP-184 in patients with advanced-stage TNBC. The study is designed to focus on dose optimization to evaluate and enhance both safety and potential efficacy ultimately aiding in the potential determination of the best clinical position for LP-184 in advanced-stage TNBC patients. The design of the dose optimization phase, provides for evaluation of the safety, efficacy and pharmacokinetics of LP-184 using 2 dose levels in an open-label monotherapy study involving around 30 patients to be dosed with LP-184. LP-184 Phase 1b/2 TNBC Trial Overview - Combination Therapy with PARP inhibitor LP-184 has also been shown in preclinical studies to be highly potent in combination with the PARP inhibitor, olaparib, including in tumors that are resistant to PARP inhibitors. In preclinical studies, treatment of a HBCx-28 TNBC PDX model, with BRCA-1 LOH and an HRD score of 63 that was resistant to the PARP inhibitor, showed evidence of re-sensitization in combination with LP-184 (See Figure 2). These data, which were initially presented at the San Antonio Breast Cancer Symposium, support the clinical evaluation of LP-184 in combination with PARPi in an earlier line of treatment. Treating patients in an earlier clinical setting has the potential to reach more patients and potentially generate a more durable and deeper earlier control of the disease. The design of the combination phase 1b/2 trial provides for LP-184 to be evaluated in a second-line setting in patients with advanced-stage TNBC whose primary tumor harbors alterations in BRCA1 or BRCA2. The primary end points of the study are expected to include safety and efficacy, with the aim of supporting a potential pathway to a regulatory approval process. Multi-Region Clinical Strategy with Focus on High-Incidence Countries The trials are planned to be conducted at select centers in the United States as well as academic cancer centers and institutions in India and Nigeria, where TNBC incidence rates are particularly high—comprising nearly 40% of initial breast cancer diagnoses. This strategic site selection is focused on leveraging established collaborative research networks that have a track record of successful collaborative cancer studies with US and European pharma companies. Lantern’s planned objective will be to ensure proper local experience and support for this clinical trial while addressing regions with significant disease burden and high clinical demand. "This IND clearance for LP-184 in a Phase 1b/2 study represents a pivotal advancement in our mission to bring precisely targeted, AI-developed medicines to patients with aggressive cancers and limited treatment options," said Panna Sharma, CEO and President of Lantern Pharma. "The strategic design of our clinical program reflects both the compelling mechanistic rationale and the encouraging data supporting LP-184's potential in TNBC." Expanding Therapeutic Potential Across Multiple Indications Beyond TNBC, LP-184 shows promise for the potential treatment of other cancers harboring DNA damage repair mutations, including lung, bladder, pancreatic, and ovarian cancers. Additional clinical trials in these targeted indications are in planning stages, with several being considered as Investigator Initiated Trials. LP-184 has received multiple Orphan Drug, Fast Track, and Rare Pediatric Disease Designations from the FDA across various solid tumor indications. The global TNBC market is estimated at $3-5 billion USD annually, with over 300,000 new cases diagnosed worldwide each year. While homologous recombination deficient TNBCs are often initially treated with PARP inhibitors, resistance inevitably develops, underscoring the critical need for novel therapeutic approaches. About Lantern Pharma Lantern Pharma (NASDAQ: LTRN) is an AI company transforming the cost, pace, and timeline of oncology drug discovery and development. Our proprietary AI and machine learning (ML) platform, RADR®, leverages over 100 billion oncology-focused data points and a library of 200+ advanced ML algorithms to help solve billion-dollar, real-world problems in oncology drug development. By harnessing the power of AI and with input from world-class scientific advisors and collaborators, we have accelerated the development of our growing pipeline of drug-candidates that span multiple cancer indications, including both solid tumors and blood cancers and an antibody-drug conjugate (ADC) program. On average, our newly developed drug programs have been advanced from initial AI insights to first-in-human clinical trials in 2–3 years and at approximately $1.0 – $2.5 million per program. Our lead development programs include a Phase 2 clinical program and multiple Phase 1 clinical trials. We have also established a wholly-owned subsidiary, Starlight Therapeutics, to focus exclusively on the clinical execution of our promising therapies for CNS and brain cancers, many of which have no effective treatment options. Our AI-driven pipeline of innovative product candidates is estimated to have a combined annual market potential of over $15 billion USD and have the potential to provide life-changing therapies to hundreds of thousands of cancer patients across the world. Forward-Looking Statements: This press release contains 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. These forward-looking statements include, among other things, statements relating to: future events or our future financial performance; the potential advantages of our RADR® platform in identifying drug candidates and patient populations that are likely to respond to a drug candidate; our strategic plans to advance the development of our drug candidates and antibody drug conjugate (ADC) development program; estimates regarding the development timing for our drug candidates and ADC development program; expectations and estimates regarding clinical trial timing and patient enrollment; our research and development efforts of our internal drug discovery programs and the utilization of our RADR® platform to streamline the drug development process; our intention to leverage artificial intelligence, machine learning and genomic data to streamline and transform the pace, risk and cost of oncology drug discovery and development and to identify patient populations that would likely respond to a drug candidate; estimates regarding patient populations, potential markets and potential market sizes; sales estimates for our drug candidates and our plans to discover and develop drug candidates and to maximize their commercial potential by advancing such drug candidates ourselves or in collaboration with others. Any statements that are not statements of historical fact (including, without limitation, statements that use words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "model," "objective," "aim," "upcoming," "should," "will," "would," or the negative of these words or other similar expressions) should be considered forward-looking statements. There are a number of important factors that could cause our actual results to differ materially from those indicated by the forward-looking statements, such as (i) the risk that we may not be able to secure sufficient future funding when needed and as required to advance and support our existing and planned clinical trials and operations, (ii) the risk that observations in preclinical studies and early or preliminary observations in clinical studies do not ensure that later observations, studies and development will be consistent or successful, (iii) the risk that our research and the research of our collaborators may not be successful, (iv) the risk that we may not be successful in licensing potential candidates or in completing potential partnerships and collaborations, (v) the risk that none of our product candidates has received FDA marketing approval, and we may not be able to successfully initiate, conduct, or conclude clinical testing for or obtain marketing approval for our product candidates, (vi) the risk that no drug product based on our proprietary RADR® AI platform has received FDA marketing approval or otherwise been incorporated into a commercial product, and (vii) those other factors set forth in the Risk Factors section in our Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission on March 27, 2025. You may access our Annual Report on Form 10-K for the year ended December 31, 2024 under the investor SEC filings tab of our website at www.lanternpharma.com or on the SEC's website at www.sec.gov. Given these risks and uncertainties, we can give no assurances that our forward-looking statements will prove to be accurate, or that any other results or events projected or contemplated by our forward-looking statements will in fact occur, and we caution investors not to place undue reliance on these statements. All forward-looking statements in this press release represent our judgment as of the date hereof, and, except as otherwise required by law, we disclaim any obligation to update any forward-looking statements to conform the statement to actual results or changes in our expectations. 1 https://ir.lanternpharma.com/news-events/press-releases/detail/171/lantern-pharmas-investigational-drug-candidate-lp-184 2 https://ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e15064 3 https://onlinelibrary.wiley.com/doi/full/10.1155/2024/8816102

Fast TrackOrphan DrugINDPhase 1

02 May 2025

·endpts.com

Drugmakers exploit cancer’s ‘lethalities’ to make next class of targeted therapies, with first results for Werner drug

CHICAGO — A new type of targeted cancer drug that blocks a “DNA caretaker” protein called Werner helicase has captured the attention of several big pharma companies in recent years, and the first data appear to reinforce its potential. Cells are typically equipped with critical redundancies for important proteins, but when they mutate in cancer patients, a single protein can become the key to a cell’s life or death. By finding the proteins that aberrant cancer cells need to function and then blocking them, drug developers are building the next generation of targeted cancer treatments. Roche now has the first data for its experimental drug, which takes advantage of what’s known as synthetic lethality, in gynecologic and colon cancers. It was shared this week at the American Association for Cancer Research’s annual meeting in Chicago. In the span of six years, scientists and physicians took a promising drug target identified via CRISPR screening and created a handful of experimental treatments for cancer patients. There are now four different Werner helicase-targeting agents in early-stage clinical trials from Roche, Novartis, GSK and Nimbus Therapeutics — a private drug developer with a track record of doing big deals. “Werner helicase really and truly represents a synthetic lethal vulnerability and therefore a therapeutic opportunity in MSI cancers,” said Timothy Yap, a physician-scientist with the University of Texas MD Anderson Cancer Center, referring to cancers with a specific DNA signature. “That’s really the crux of it and why it was so exciting.” Synthetic lethality is a phenomenon that scientists are exploiting to develop new targeted cancer treatments. Their inspiration is PARP inhibitors (such as AstraZeneca’s Lynparza), a class of drugs used to treat a wide range of cancers including breast and ovarian. PARP inhibitors are a synthetic lethal therapy for cancers with BRCA mutations. In the Phase 1 study, Roche’s experimental drug led to four confirmed responses — two in endometrial cancer, one in colorectal cancer, and one in ovarian cancer — in 35 patients. There was also a fifth unconfirmed response in endometrial cancer. Yap presented the data Sunday at the AACR meeting. The responses mean the drug, which came from Roche’s partnership with Vividion Therapeutics in 2020, shrank the tumors in these patients at least 30%. It’s the first time that researchers have shown the effect of a Werner helicase blocker in people. Many of the patients in the study had gone through several previous treatment regimens. While their cancers were found in a wide range of locations, most of the tumors were considered microsatellite instable, which is a sign of DNA misrepair that physicians frequently look for in cancer diagnoses. The initial science that identified Werner helicase as a potential target showed that knocking it out was lethal to the microsatellite instable cells, and this piqued the interest of drug developers. Microsatellite instability-high cancers make up around 3% of all cancer cases, according to some estimates. The responses to Roche’s drug occurred at a range of doses, from 150 mg a day to 1,000 mg twice a day. In an interview, Ryan Corcoran, director of the gastrointestinal cancer center program at the Massachusetts General Hospital Cancer Center, said there’s not a clear correlation between the responses and dose levels. Researchers typically look for dose dependency (more drug equals better efficacy) in clinical studies as a green flag the treatment is working as intended. Corcoran, who chaired the session where Roche’s clinical trial results were presented, consults for Roche but not on the Werner helicase project. The primary side effects related to the drug were nausea, vomiting and diarrhea. There were no dose-limiting toxicities. Like Novartis had already reported, both GSK and Nimbus disclosed at the meeting that their molecules were non-covalent, meaning they do not permanently bind Werner helicase. This leaves Roche as the lone company developing a covalent, or permanently binding, agent in clinical trials. GSK suggested in its presentation that its drug could work in tumors that acquired resistance to Roche or Novartis’ compounds, but that’s based on animal model data and has not been shown in humans. GSK’s drug comes from a partnership with Ideaya Biosciences, a biotech company that’s focused on developing drugs against synthetic lethalities. In 2019, four papers were published showing Werner helicase could be a promising target for treating microsatellite instable cancers. These cancers tend to respond well to immunotherapy, but patients have few other options beyond those treatments. Of the two studies published in Nature on the same day, one was from Mathew Garnett’s lab at the Wellcome Sanger Institute, while the other was led by Adam Bass, who at the time was at the Dana-Farber Cancer Institute and now leads translational cancer research at Novartis. Using CRISPR screening, researchers from both groups found that Werner helicase was needed in microsatellite instable cancer models but dispensable in models that were microsatellite stable. “When you knock out Werner helicase, in 48 hours, the cells are dead,” Garnett said. “All their DNA is just shattered, and it’s really phenomenal. You had this sense when you saw this genome shattering, that there was something really profound happening to these cells.” There are several other synthetic lethality programs in early-stage trials. Corcoran said he has yet to see results from another class of synthetic lethal drugs that matches the success of PARP inhibitors, though many of these efforts are still early and have yet to report clinical data. One closely-watched effort to leverage synthetic lethality is targeting a protein called PRMT5 in cancers with mutations known as MTAP deletions. This is an area in which Bristol Myers Squibb, Amgen, Ideaya and others are all working on early-stage programs, though readouts so far have been mixed . Eli Lilly and Foghorn Therapeutics last year began a Phase 1 trial for a SMARCA2 inhibitor, which they are studying in patients with SMARCA4-mutated cancers. “Imagine you’re riding a bicycle — it’s a bicycle with two wheels — and one of the wheels is lost, and now you’re riding a unicycle,” Foghorn CEO Adrian Gottschalk said. And so giving a SMARCA2 inhibitor to one of these patients is like taking a stick to the cancer cell’s remaining wheel, he said.

AACRPhase 1

100 Deals associated with Olaparib

External Link

KEGG	Wiki	ATC	Drug Bank
D09730	Olaparib	L01XX46	DB09074

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Advanced Endometrial Carcinoma	European Union	AstraZeneca AB	15 Aug 2024
Advanced Endometrial Carcinoma	Iceland	AstraZeneca AB	15 Aug 2024
Advanced Endometrial Carcinoma	Liechtenstein	AstraZeneca AB	15 Aug 2024
Advanced Endometrial Carcinoma	Norway	AstraZeneca AB	15 Aug 2024
Recurrent Endometrial Cancer	European Union	AstraZeneca AB	15 Aug 2024
Recurrent Endometrial Cancer	Iceland	AstraZeneca AB	15 Aug 2024
Recurrent Endometrial Cancer	Liechtenstein	AstraZeneca AB	15 Aug 2024
Recurrent Endometrial Cancer	Norway	AstraZeneca AB	15 Aug 2024
BRCA mutation positive Breast Cancer	Japan	AstraZeneca KK	24 Aug 2022
HRD-positive Ovarian Cancer	United States	AstraZeneca Pharmaceuticals LP	19 May 2020
HRR Gene-mutated Castration-Resistant Prostate Cancer	United States	AstraZeneca Pharmaceuticals LP	19 May 2020
Pancreatic Cancer	South Korea	AstraZeneca Pharmaceuticals LP	29 Oct 2019
Prostatic Cancer	South Korea	AstraZeneca Pharmaceuticals LP	29 Oct 2019
Platinum-Sensitive Ovarian Carcinoma	China	AstraZeneca AB	22 Aug 2018
Recurrent HER2-Negative Breast Carcinoma	Japan	AstraZeneca KK	02 Jul 2018
Recurrent HER2-Negative Breast Carcinoma	Japan	MSD KK	02 Jul 2018
Pancreatic adenocarcinoma metastatic	Australia	AstraZeneca Pty Ltd.	23 May 2018
Breast Cancer	Canada	AstraZeneca Canada, Inc.	29 Apr 2016
Ovarian Cancer	Canada	AstraZeneca Canada, Inc.	29 Apr 2016
BRCA Mutation Castration-Resistant Prostate Cancer	European Union	AstraZeneca AB	16 Dec 2014

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Castration-Resistant Prostatic Cancer	NDA/BLA	United States	AstraZeneca PLC	17 Aug 2022
Endometrial Carcinoma	Phase 3	France	AstraZeneca PLC	26 Jun 2024
Ovarian Serous Adenocarcinoma	Phase 3	United States	Novartis Pharmaceuticals Corp.	22 Jul 2021
Ovarian Serous Adenocarcinoma	Phase 3	China	Novartis Pharmaceuticals Corp.	22 Jul 2021
Ovarian Serous Adenocarcinoma	Phase 3	Argentina	Novartis Pharmaceuticals Corp.	22 Jul 2021
Ovarian Serous Adenocarcinoma	Phase 3	Australia	Novartis Pharmaceuticals Corp.	22 Jul 2021
Ovarian Serous Adenocarcinoma	Phase 3	Austria	Novartis Pharmaceuticals Corp.	22 Jul 2021
Ovarian Serous Adenocarcinoma	Phase 3	Belgium	Novartis Pharmaceuticals Corp.	22 Jul 2021
Ovarian Serous Adenocarcinoma	Phase 3	Brazil	Novartis Pharmaceuticals Corp.	22 Jul 2021
Ovarian Serous Adenocarcinoma	Phase 3	Canada	Novartis Pharmaceuticals Corp.	22 Jul 2021

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03741426 (WIRE, AACR2025)	Phase 2	Kidney Neoplasms Neoadjuvant	29	Cediranib	bufhzwqpkq(wolpsotmwd) = 6 (100%) vs 14 (88%) vs 6 (86%) timaisvsbi (gmpskaituz ) View more	Positive	29 Apr 2025
NCT03741426 (WIRE, AACR2025)	Phase 2	Kidney Neoplasms Neoadjuvant	29	Cediranib & Olaparib		Positive	29 Apr 2025
NCT04483544 (CTgov)	Phase 2	Fanconi Anemia \| Advanced Cervical Carcinoma	8	olaparib+pembrolizumab	xpaxrkjigy = cnsymdkxiv giefitrvil (jybkfqgmhk, niybljxtbu - awxkvyeqel) View more	-	29 Apr 2025
NCT03991832 (Phase II trial, AACR2025)	Phase 2	Glioma cfDNA methylome	29	Olaparib 300 mg twice daily + Durvalumab 1500 mg IV every 4 weeks	uijobtaqed(jiokiurlji) = cgcmosxmqt undopjxjze (nckmiefbar, 2.2 - 27)	Positive	28 Apr 2025
NCT04123366 (KEYLYNK-007, AACR2025) Manual	Phase 2	HRD positive cancer Homologous Recombination Deficiency Positive	332	Olaparib 300 mg BID + Pembrolizumab 200 mg Q3W (BRCA 1/2m)	arwkaamnrj(zswitkjspb) = qykmevkeme yajvollyxi (vuqkbfhhxl, 19.9 - 35.7) View more	Positive	27 Apr 2025
NCT04123366 (KEYLYNK-007, AACR2025) Manual	Phase 2		332	Olaparib 300 mg BID + PembrolizumabPembrolizumab 200 mg Q3W (non-BRCA HRRm)	arwkaamnrj(zswitkjspb) = cpohsqujno yajvollyxi (vuqkbfhhxl, 6.1 - 19.3) View more	Positive	27 Apr 2025
NCT03953898 (CTgov)	Phase 2	Relapsing acute myeloid leukemia \| Treatment related acute myeloid leukaemia \| Refractory Myelodysplastic Syndrome ... View more	14	Bone Marrow Aspiration+Olaparib	gwdilzzlcq(fewisgnkmw) = kokvztjupg wnuofkiqcq (oogrqqyyhg, bbwaoxdayp - cypitcuquy) View more	-	30 Mar 2025
ASCO_GU2025	Not Applicable	Metastatic castration-resistant prostate cancer AR-PV \| AR-A	142	Olaparib monotherapy	wznrpnvnvx(mubearwgyg) = For mCRPC patients receiving combined therapy, the average AR-A group exhibited better PFS and OS compared to the lower AR-A group (median PFS: 7 months vs 3 months; median OS: 17 months vs 10 months) jvhcbqvohe (sbmblgmrsf ) View more	Positive	13 Feb 2025
ASCO_GU2025	Not Applicable		142	Combined therapy (Olaparib + Abiraterone)		Positive	13 Feb 2025
NCT03976323 (KEYLYNK-006 \| MK-7339-006, CTgov)	Phase 3	Metastatic Non-Squamous Non-Small Cell Lung Carcinoma	1,003	Olaparib+Pembrolizumab (Pembrolizumab + Olaparib (Maintenance Phase))	ljlmqdvzmi(ukgefmerbj) = ippcabotsa aaxlwsfvuz (ljfsocttda, jbbyxchknp - iajrtusyjy) View more	-	06 Feb 2025
NCT03976323 (KEYLYNK-006 \| MK-7339-006, CTgov)	Phase 3	Metastatic Non-Squamous Non-Small Cell Lung Carcinoma	1,003	Pemetrexed+Pembrolizumab (Pembrolizumab + Pemetrexed (Maintenance Phase))	ljlmqdvzmi(ukgefmerbj) = snmpdmttwr aaxlwsfvuz (ljfsocttda, bwwhsrotks - cfjsmcthru) View more	-	06 Feb 2025
NCT05501548 (CTgov)	Phase 2	Castration-Resistant Prostatic Cancer \| Metastatic castration-resistant prostate cancer	4	Olaparib+Vitamin C	adoohdpcbl = eiazcrllsy gzjsdluggv (mojixekvmn, rfbbhvlhws - ohvnhrozpk) View more	-	29 Jan 2025
NCT04538378 (CTgov)	Phase 2	Adenocarcinoma \| Small Cell Carcinoma \| Small Cell Lung Cancer ... View more	4	Tumor biopsy+Olaparib+Durvalumab	lumjdbcmem = eafwtxbfqy hirzvwtbxd (zqlzguiuuz, jxvnbalnsu - jnmwslygvv) View more	-	27 Jan 2025
NCT03829345 (SOlar, ASCO_GI2025)	Phase 2	Gastrooesophageal junction cancer deficient DNA damage repair \| HER2-positive	55	Olaparib 300mg twice daily	rdzodcnhtx(yxjhtlfcpv) = stcggqybgj cywsjmorns (bwifhenrxl, 19.4)	Positive	23 Jan 2025

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