On September 11, 2023 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage precision oncology company developing therapies that target families of oncogenic mutations in patients with genetically defined cancers, reported the first patients dosed in mutation matched expansion cohorts of non-small cell lung cancer (NSCLC) in the ongoing Phase 1 clinical study evaluating BDTX-1535 (Press release, Black Diamond Therapeutics, SEP 11, 2023, View Source [SID1234635058]).

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BDTX-1535, a fourth-generation, brain-penetrant epidermal growth factor receptor (EGFR) MasterKey tyrosine kinase inhibitor (TKI), is under investigation for the treatment of NSCLC harboring intrinsic driver and/or acquired resistance (post-osimertinib) EGFR mutations and glioblastoma multiforme (GBM) with multiple EGFR alterations. The BDTX-1535 expansion cohort portion of the study will assess single-agent objective response rate (ORR) in a second- or third-line setting in NSCLC patients with EGFR intrinsic driver and/or acquired resistance mutations, who have received prior treatment with approved EGFR TKI.

The dosing of the first patients in the expansion cohorts follows the Company’s initial data readout from the dose escalation portion of the BDTX-1535 Phase 1 clinical study, which demonstrated clinical proof of activity through radiographic responses in NSCLC patients harboring diverse types of EGFR mutations including intrinsic driver and post-osimertinib acquired resistance EGFR mutations.

"The Phase 1 expansion cohorts will assess objective response rate and durability of response in NSCLC patients whose disease has progressed after prior EGFR inhibitor therapy, including prior osimertinib, and who have evidence of a variety of EGFR driver or resistance mutations that are targeted by BDTX-1535," said Sergey Yurasov, M.D., Ph.D., Chief Medical Officer of Black Diamond Therapeutics. "In conjunction with establishing an optimal dose for a future pivotal study, these efficacy data will be essential for establishing a regulatory pathway for BDTX-1535. Despite significant recent advances in treating lung cancer, there is a large unmet medical need for a targeted therapy for these EGFR mutation-positive NSCLC patients, for whom chemotherapy is still the most common treatment option."

"Dosing of the first patients in the BDTX-1535 dose expansion cohorts represents an important step towards offering an oral therapeutic with manageable side effects as a potential alternative to chemotherapy-based regimens following progression on osimertinib for patients with treatment-resistant lung cancer," said David Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "The population of EGFR mutation-positive NSCLC is genetically heterogeneous – which has presented challenges in the development of effective therapies. BDTX-1535 was designed to disrupt the limited existing treatment paradigm by addressing real-world patterns of patient-specific EGFR mutations, and we remain focused on the rapid advancement of this novel MasterKey inhibitor."

The discovery and development of BDTX-1535 was informed by the Company’s powerful Mutation-Allostery-Pharmacology (MAP) drug discovery engine, which leverages critical genomic profiling to expand the addressable patient population by targeting families of mutations with a single drug. Emergence of intrinsic driver and acquired resistance EGFR mutations to osimertinib represents a significant unmet need for patients with EGFR-mutant lung cancer. Thirteen percent of patients in the U.S. with EGFR mutation-positive NSCLC show presence of intrinsic driver mutations, which are associated with worse clinical outcomes when treated with currently approved EGFR TKIs. Fifteen percent of patients in the U.S. whose disease has progressed after osimertinib therapy show evidence of acquired resistance EGFR mutations (e.g., C797S) for which currently there is no approved EGFR TKI.

The Company is advancing BDTX-1535 as a potential targeted therapy option for patients with this broad spectrum of EGFR mutations in second-line NSCLC, and plans to investigate safety and efficacy in a first-line setting in NSCLC patients with intrinsic driver EGFR mutations after discussion with the U.S. Food and Drug Administration (FDA).

BDTX-1535 Phase 1 Clinical Study Design
The Phase 1 first-in-human, open-label clinical trial of BDTX-1535 (NCT05256290) consists of a dose escalation portion that evaluated the safety, pharmacokinetics (PK), and preliminary anti-tumor activity of BDTX-1535 followed by dose expansion cohorts. The trial is evaluating BDTX-1535 in patients with advanced/metastatic NSCLC harboring EGFR mutations with or without central nervous system (CNS) disease, or with recurrent GBM expressing EGFR alterations. The Phase 1 dose escalation portion of the study in NSCLC and GBM patients has been completed and the study is now progressing to evaluate BDTX-1535 as a single agent, second-line or third-line therapy in two cohorts of EGFR mutation-positive NSCLC patients with progressive disease after prior therapy with EGFR TKI (e.g., osimertinib) to assess ORR, CNS ORR, duration of response, and progression-free survival and further evaluate safety, tolerability and PK:

Second- or third-line NSCLC patients with acquired EGFR resistance mutations +/- CNS metastasis; and
Second- or third-line NSCLC patients with EGFR intrinsic driver mutations +/- CNS metastasis.

On September 11, 2023 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a commercial stage biopharmaceutical company focused on certain cancers and rare diseases, reported that the U.S. Food and Drug Administration (FDA) has approved APHEXDA (motixafortide) in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma (Press release, BioLineRx, SEP 11, 2023, View Source [SID1234635057]). APHEXDA is administered by injection, for subcutaneous use.

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Multiple myeloma is the second most-common hematologic malignancy. Autologous stem cell transplantation (ASCT) is part of the standard of care treatment paradigm for multiple myeloma and delivers prolonged survival for patients with this cancer type.1 The success of ASCT depends on adequate mobilization of stem cells during the treatment process. The American Society for Transplantation and Cellular Therapy (ASTCT) guidelines recommend a collection target of 3-5 x 106 CD34+ cells/kg.2 Additionally, collection of a sufficient number of stem cells to perform two transplantations is recommended.2-5 Historically, depending on induction regimens and mobilization strategies, up to 47% of patients have had challenges collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session.6-7

"Greater numbers of patients with multiple myeloma are candidates for autologous stem cell therapy; however, achieving target collection goals can be difficult in some patients given modern barriers, including the treatment of older patients and use of contemporary induction regimens," said John DiPersio, MD, PhD, primary investigator for the GENESIS trial and

Professor of Medicine, Pathology and Immunology and Director of the Center for Gene and Cellular Immunotherapy at Washington University School of Medicine in St. Louis. "Innovation in this area of medicine has been needed, and today’s approval of APHEXDA addresses the demand for new therapies that can meet today’s challenges by delivering more reliability in stem cell mobilization, versus filgrastim alone, with fewer days of apheresis sessions and fewer doses of filgrastim for people living with this cancer."

The FDA approval of APHEXDA is based on results from the 2-part, Phase 3 GENESIS trial, a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim, compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study.8

The assessment of CD34+ cells was performed by central and local laboratories. Central laboratory assessments were used for the efficacy results. Local laboratory results were used for clinical treatment decisions. APHEXDA plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of ≥ 6 × 106 CD34+ cells/kg within two apheresis sessions, versus 9.5% for the placebo plus filgrastim regimen, as measured by central laboratory.9 Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the APHEXDA arm and 21.4% in the placebo arm, as measured by local laboratories.9 Local laboratory data were used for a sensitivity analysis. The data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted.

In GENESIS, the safety was evaluated in 92 patients with multiple myeloma who received APHEXDA 1.25 mg/kg subcutaneously plus filgrastim, and 42 patients who received placebo plus filgrastim. Serious adverse reactions occurred in 5.4% of patients receiving APHEXDA plus filgrastim. These reactions included vomiting, injection site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia and hypoxia. The most common adverse reactions occurring in GENESIS (incidence >20%) were injection site reactions (pain, erythema and pruritus), pruritus, flushing, and back pain.9

"Given the strong efficacy data shown in the GENESIS trial, which included patients who are representative of the current multiple myeloma patient population, we believe APHEXDA will play a critical role in addressing unmet needs and introduce a new treatment paradigm for this challenging cancer," said Philip Serlin, Chief Executive Officer of BioLineRx Ltd. "The company is working relentlessly to make this important innovation in stem cell mobilization available to appropriate patients, their physicians and transplant teams."

"FDA approval of APHEXDA, the company’s first approved therapeutic, is a tremendously exciting and important moment in our history and validates our drug development programs," said Ella Sorani, PhD, Chief Development Officer of BioLineRx Ltd. "We would like to thank all of the patients and families who have contributed to the research and development of APHEXDA."

Increased age, as well as exposure to lenalidomide-containing induction regimens, including 3-4 drug combination regimens, have been associated with impaired stem cell mobilization.2-3 The GENESIS study included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with ~70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.8 In this contemporary population, patients in the APHEXDA plus filgrastim arm were able to mobilize more than four times the amount of stem cells with a single dose over a 24-hour period compared with placebo plus filgrastim.8

BioLineRx expects to make APHEXDA available later this month. For further information about APHEXDA, please see the Important Safety Information below and the full Prescribing Information, and visit www.APHEXDA.com.

APHEXDA Investor Conference Call
The Company will host an investor conference call on September 12, 2023 at 8:00 a.m. EDT featuring remarks by Philip Serlin, Chief Executive Officer.

To access the conference call, please dial +1-888-281-1167 from the U.S. or +972-3-918-0685 internationally. A live webcast and a replay of the call can be accessed through the event page on the Company’s website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast. The call replay will be available approximately two hours after completion of the live conference call. A dial-in replay of the call will be available until September 14, 2023; please dial +1-888-295-2634 from the US or +972-3-925-5904 internationally.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow. According to the American Cancer Society, in 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and nearly 13,000 people will die from the disease in the U.S.10 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections.

About Autologous Stem Cell Transplantation
Autologous stem cell transplantation (ASCT) is part of the standard treatment paradigm for a number of blood cancers, including multiple myeloma. In the U.S., as many as 8,000 ASCTs are performed each year in patients with multiple myeloma.11 The current ASCT standard of care includes 4-6 cycles of induction therapy (an initial drug-combination regimen to position the patient for as deep a treatment response as possible). To begin the stem cell mobilization process, a patient will receive a daily dose of filgrastim (G-CSF) for four days. Daily doses of filgrastim will continue until the target collection goal is met with the addition of up to four daily doses of plerixafor as needed.12 For patients unable to mobilize sufficient numbers of cells for harvesting during this primary mobilization phase, rescue therapy may be carried out followed by an additional number of apheresis sessions as necessary.2

About the GENESIS Trial
GENESIS (NCT 03246529) is a 2-part, Phase-3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim (G-CSF), compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study.8

The primary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in one apheresis session.8

The study met the primary endpoint with a high degree of statistical significance (p<0.0001). The assessment of CD34+ cells was performed by central and local laboratories. Central laboratory assessments were used for the efficacy results. Local laboratory results were used for clinical treatment decisions. APHEXDA plus filgrastim enabled 67.5% of patients to achieve the cell collection goal of ≥ 6 × 106 CD34+ cells/kg in up to two apheresis sessions with a single administration, versus 9.5% for the placebo plus filgrastim regimen, as measured by central laboratory.9 Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the APHEXDA arm and 21.4% in the placebo arm, as measured by local laboratories.13 Local laboratory data were used for a sensitivity analysis. The data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted.

The safety of APHEXDA was evaluated in 92 patients with multiple myeloma who received APHEXDA 1.25 mg/kg subcutaneously plus filgrastim and 42 patients who received placebo plus filgrastim for mobilization of hematopoietic stem cells for collection and apheresis. Serious adverse reactions occurred in 5.4% of patients receiving APHEXDA plus filgrastim. Serious adverse reactions included vomiting, injection site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia and hypoxia. The most common adverse reactions occurring in GENESIS (incidence >20%) were injection site reactions (pain, erythema, and pruritus), pruritus, flushing and back pain.9

Please see important safety information below.

About APHEXDA
APHEXDA (motixafortide) is a CXCR4 antagonist with long receptor occupancy (greater than 72 hours) that, in combination with filgrastim (G-CSF), enables mobilization of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous stem cell transplantation in patients with multiple myeloma.9

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION
APHEXDA is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
APHEXDA is contraindicated in patients with a history of serious hypersensitivity reactions to motixafortide.

WARNINGS AND PRECAUTIONS

Anaphylactic Shock and Hypersensitivity Reactions: Anaphylactic shock and hypersensitivity reactions have occurred. Premedicate all patients with a triple drug premedication regimen that includes an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor approximately 30-60 minutes prior to each dose of APHEXDA. Administer APHEXDA in a setting where personnel and therapies are immediately available for treatment of anaphylaxis and other systemic reactions. Monitor patients for 1 hour following APHEXDA administration and manage reactions promptly. Patients receiving negative chronotropic drugs (e.g., beta-blockers) may be more at risk for hypotension in the event of a hypersensitivity reaction and these drugs, when appropriate, should be replaced with non-chronotropic drugs.
Injection Site Reactions: Injection site reactions (73%) including pain (53%), erythema (27%), and pruritus (24%) have occurred. Severe reactions occurred in 9% of patients. Premedicate with an analgesic premedication (e.g., acetaminophen) prior to each APHEXDA dose. Use analgesic medication and local treatments post-dose, as needed.
Tumor Cell Mobilization in Patients with Leukemia: For the purpose of hematopoietic stem cell (HSC) mobilization, APHEXDA may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, APHEXDA is not intended for HSC mobilization and harvest in patients with leukemia.
Leukocytosis: Administering APHEXDA in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during APHEXDA use.
Potential for Tumor Cell Mobilization: When APHEXDA is used in combination with filgrastim for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.
Embryo-fetal Toxicity: Based on its mechanism of action, APHEXDA can cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating treatment with APHEXDA and advise use of effective contraception during treatment and for 8 days after the final dose.
ADVERSE REACTIONS
The most common adverse reactions (incidence >20%) in patients treated with APHEXDA were injection site reactions [73%, including pain (53%), erythema (27%), pruritus (24%)]; pruritus (38%); flushing (33%); back pain (21%).

USE IN SPECIFIC POPULATIONS

Pregnancy: Please see the important information in Warnings and Precautions under Embryo-fetal Toxicity.

Lactation: There are no data on the presence of motixafortide in human milk, the effects on the breastfed child, or the effects on milk production. Advise females that breastfeeding is not recommended during treatment with APHEXDA and for 8 days after the final dose.

Pediatric Use: The safety and effectiveness of APHEXDA have not been established in pediatric patients.

Please see the accompanying full Prescribing Information.

On September 11, 2023 Bicycle Therapeutics (Nasdaq: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that the company will proceed with its plan to expedite development of BT8009 for metastatic bladder (urothelial) cancer following recent discussions with the U.S. Food and Drug Administration (FDA) (Press release, Bicycle Therapeutics, SEP 11, 2023, View Source [SID1234635056]). The company has aligned with the FDA on a Phase 2/3 registrational trial, called Duravelo-2, that has an innovative design allowing for potential accelerated approval in untreated (first-line) and previously treated (second-line plus) metastatic bladder cancer. The company plans to initiate the Duravelo-2 trial in the first quarter of 2024.

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"We prepared a robust and innovative clinical development plan for BT8009, with the goal of getting this much-needed therapy to patients as quickly as possible. We are pleased to have reached alignment with the FDA on the registrational trial design, dose selection and clinical trial endpoints that could support potential accelerated approval in a broad metastatic bladder cancer population," said Santiago Arroyo, M.D., Ph.D., chief development officer at Bicycle Therapeutics. "In preparation for this positive outcome, we have put in place the clinical infrastructure that will allow us to start the registrational trial early next year."

The Phase 2/3 Duravelo-2 trial will assess BT8009 in untreated metastatic bladder cancer (Cohort 1) and previously treated metastatic bladder cancer (Cohort 2). In Cohort 1, two doses of BT8009 plus standard pembrolizumab regimen will be initially assessed. Following selection of the optimal dose, BT8009 plus pembrolizumab will be evaluated against chemotherapy. Potential accelerated approval will be determined by objective response rate (ORR), and progression-free survival (PFS) will be used to confirm clinical benefit.

In Cohort 2, two doses of BT8009 as monotherapy will be initially studied. Following selection of the optimal dose, an additional arm of BT8009 plus standard pembrolizumab regimen will be added. Potential accelerated approval for BT8009 monotherapy and in combination with pembrolizumab will be determined by ORR compared to historical control data. Discussions with the FDA about the design of the confirmatory trial for previously treated metastatic bladder cancer are ongoing.

"At Bicycle Therapeutics, we are committed to using our novel platform to develop precision targeted therapeutics and improve the lives of patients who are battling devastating diseases. This is why, in line with the philosophy of the FDA’s Project FrontRunner and following the agency’s recent draft guidance on accelerated approval of oncology therapeutics, we have initially focused on defining the regulatory path for BT8009 in untreated patients. We believe today’s announcement is good news for patients, and we are greatly appreciative of the FDA for their collaboration and guidance," said Kevin Lee, Ph.D., chief executive officer of Bicycle Therapeutics. "As we look to the rest of 2023, we continue to make progress in our research and development programs and look forward to providing updates on BT8009, BT5528 and BT7480 later this year."

Conference Call and Webcast Information
Bicycle Therapeutics will host a conference call and webcast today, September 11, 2023, at 8 a.m. ET to review the BT8009 regulatory update. To access the call, please dial 1-833-816-1408 (U.S.) or +1 412-317-0501 (international) and ask to be joined into the Bicycle Therapeutics call. A live webcast and replay of the conference call will be available in the Investor section of the Bicycle website, bicycletherapeutics.com.

About BT8009
BT8009 is an investigational Bicycle Toxin Conjugate (BTC) targeting Nectin-4, a well-validated tumor antigen with elevated levels of expression in multiple tumor types, including bladder (urothelial) cancer. It is currently being evaluated in a Phase 1/2 clinical trial enrolling patients with Nectin-4 expressing advanced solid tumors. BT8009 will be evaluated in the Phase 2/3 Duravelo-2 trial, a global, multi-center, adaptive study designed to assess the safety and efficacy of the therapy for metastatic bladder cancer.

On September 11, 2023 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical stage biopharmaceutical company focused on precision oncology through synthetic lethality, reported updated preclinical data supporting development of the Company’s WEE1 inhibitor candidate, ATRN-1051, for the treatment of ovarian cancer (Press release, Aprea, SEP 11, 2023, View Source [SID1234635055]).

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The preclinical and in vitro data suggest that the selective properties of ATRN-1051 may make it a more efficacious cancer therapy than the other WEE1 inhibitors in development. Importantly, ATRN-1051 is a highly potent and selective inhibitor of WEE1 that does not significantly affect off-target PLK1, PLK2 and PLK3, a family of kinases that promote M phase entry, a critical phase in the cell cycle. Such off-targeting of the PLK family has been a challenge to other WEE1 inhibitors in the class. Evidence generated by Aprea suggests that off-target inhibition of PLK1 substantially limits the ability of WEE1 inhibitors to cause genotoxicity, the proposed mechanism by which WEE1 inhibitors act as cancer therapeutics.

The preclinical research of ATRN-1051 in ovarian cancer also shows an increased expression of cyclin E1, or CCNE1. CCNE1 amplification, which is associated with platinum resistance and poor survival, has been shown to be a reliable predictive biomarker of response to WEE1 inhibition. As part of the preclinical studies with ATRN-1051, the Company conducted cell culture and CDX mouse model studies using the CCNE1-normal and CCNE1-amplified ovarian cancer cell lines to show that low doses of ATRN-1051 completely suppress the growth of CCNE1-amplified ovarian cancer cells and tumors. In addition to the anti-tumor activity, the preclinical studies of ATRN-1051 indicate improved AUC pharmacokinetic properties compared to other WEE1 inhibitors, with the low dose of ATRN-1051 showing a similar AUC as higher doses of other WEE1 inhibitors.

Table 1
ATRN 1051 (1) Zentalis AstraZeneca
ZN-c3 (2) AZD-1775 (2)
Dose (mg/kg/d) 10 20 40 80 20 40 80
Cmax ng/ml 1,460 1,167 1,997 5,100 635 2,460 4,703
Tmax hr 3 1 1 1 1 1 1
AUC0-24, ng*hr/ml 16,739 4,863 17,088 39,722 1,494 6,313 13,408

Note: Head-to-head studies have not been conducted
(1) Data from an exploratory formulation of ATRN-1051 administered to fasted Balb/c mice
(2) Data from study in A-427 NSCLC xenograft model as reported in Zentalis Corporate Overview, March 2022

"We are very excited and encouraged by these positive findings that demonstrate ATRN-1051’s promise as a clinical agent based on its preclinical in vivo activity and safety profile," said Dr. Oren Gilad, President and CEO of Aprea. "We look forward to presenting the full data set at an upcoming 2023 scientific conference and to filing an IND for ATRN-1051 by the end of 2023. We believe these findings support the further development of this potentially substantial and clinically important agent. We also look forward to hosting a key opinion leader (KOL) event this fall highlighting these exciting data and outlining our development plan."

WEE1 kinase is a key regulator of multiple phases of the cell cycle, most prominently in progression from G1 to S phase and S to M phase through inhibitory phosphorylation of CDK2 and CDK1, respectively. Thus, when WEE1 is inhibited, both G1-S and S-M checkpoints are abrogated, leading to premature S-phase and M-phase entry. Notably, the replication stress caused by CCNE1 overexpression is transformed into toxic levels of double stranded breaks and cancer cell death when WEE1 is inhibited. The Company believes that CCNE1 gene amplification or high CCNE1 protein expression is a potential predictive biomarker of ATRN-1051 efficacy.

About ATRN-1051
The Company is targeting the WEE1 kinase, a key regulator of multiple phases of the cell cycle, with its lead WEE1 inhibitor product candidate, ATRN-1051. ATRN-1051 is an orally bioavailable small molecule inhibitor of WEE1 that is highly potent and selective. ATRN-1051 is distinct from other WEE1 inhibitors based on its potentially superior pharmacokinetic properties and selectivity. The company anticipates filing an IND for ATRN-1051 by the end of 2023.

On September 11, 2023 Amgen (NASDAQ:AMGN) reported that it will present at the Bank of America Merrill Lynch Global Healthcare Conference at 11:40 a.m. BST on Thursday, Sept. 14, 2023 (Press release, Amgen, SEP 11, 2023, View Source [SID1234635054]). Peter H. Griffith, executive vice president and chief financial officer at Amgen will present at the conference. The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

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The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.