On May 14, 2024 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported financial results for the first quarter ended March 31, 2024, and provided a corporate update (Press release, Candel Therapeutics, MAY 14, 2024, View Source [SID1234643211]).

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"It was a catalyst-rich first quarter for Candel, marked by significant advances across both our clinical and preclinical programs," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "Notably, as our clinical data mature with long-term follow up, we are beginning to observe highly differentiated results in long-term survival of patients treated with our viral immunotherapies. An example of these clinical results was recently shared in an update of the phase 2 randomized clinical trial of CAN-2409 in patients with borderline resectable pancreatic cancer, where a notable improvement in overall survival, in patients treated with CAN-2409 plus standard of care chemoradiation, was demonstrated compared to chemoradiation alone. The FDA granted CAN-2409 both Fast Track Designation and Orphan Drug Designation for treatment of patients with pancreatic ductal adenocarcinoma to improve median overall survival and treatment of pancreatic cancer, respectively, providing steady momentum to advance this promising investigational treatment for patients with significant unmet medical need."

Dr. Tak continued, "We are also excited to announce that topline overall survival data from our phase 2 clinical trial of CAN-2409 in patients with stage III/IV non-small cell lung cancer and an inadequate response to immune checkpoint inhibitors will be presented at the upcoming ASCO (Free ASCO Whitepaper) meeting in Chicago on Monday, June 3, 2024."

"In addition to our advances in the clinic, we have made great progress with our enLIGHTENTM Discovery Platform. In April 2024, we presented our second drug candidate from this platform, a first-in-class multimodal immunotherapy candidate for induction of tertiary lymphoid structures, in a late-breaking presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. We believe this preclinical candidate offers groundbreaking potential in the treatment of cancer," continued Dr. Tak. "We expect to release additional preclinical and clinical data in the coming year, consistent with our commitment to innovation and patient care."

First Quarter 2024 & Recent Highlights

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Program Updates

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CAN-2409 – Pancreatic Cancer

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In early April, announced positive updated survival data, from the ongoing randomized phase 2 clinical trial of CAN-2409 plus valacyclovir (prodrug), together with standard of care (SoC) chemoradiation, followed by resection for borderline resectable pancreatic ductal adenocarcinoma (PDAC).

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Data showed notable improvements in estimated median overall survival (mOS) of 28.8 months after experimental treatment with CAN-2409 versus 12.5 months in control group.

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At 24 months, survival rate was 71.4% in CAN-2409 treated patients versus 16.7% in the control group after chemoradiation. At 36 months, estimated survival was 47.6% in the CAN-2409 group versus 16.7% in the control group.

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No new safety signals were observed, providing further support that multiple injections of CAN-2409 have been generally well tolerated to date, with no dose-limiting toxicities and no cases of pancreatitis reported.

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Previous analysis of resected tumors showed dense aggregates of immune cells, including CD8+, cytotoxic tumor infiltrating lymphocytes and dendritic cells, in PDAC tissue after CAN-2409 administration, confirming activation of a robust antitumoral immune response.

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Received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for CAN-2409 for the treatment of pancreatic cancer.

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CAN-2409 – Non-small cell lung cancer (NSCLC)

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Announced a poster titled "Overall survival after treatment with CAN- 2409 plus valacyclovir in combination with continued ICI in patients with stage III/IV NSCLC with inadequate response to ICI" was accepted for the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, and will be presented by Charu Aggarwal, MD, MPH, Associate Professor for Lung Cancer Excellence, Perelman School of Medicine, University of Pennsylvania, on June 3, 2024 in Chicago, IL.

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CAN-3110 – Recurrent High-Grade Glioma (rHGG)

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Received Fast Track Designation from the FDA for CAN-3110 for the treatment of patients with rHGG to improve OS.

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Announced during the 5th Glioblastoma Drug Development Summit in Boston that six patients have been treated with multiple injections (up to six injections) of CAN-3110 in cohort C of the ongoing phase 1b clinical trial, reporting a favorable safety and tolerability profile.

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Announced a Trial-in-Progress poster, titled "Longitudinal stereotactic injections of oncolytic immunoactivating rQNestin34.5v.2 (CAN-3110) with concomitant biopsies for "-omic" analyses in recurrent glioblastoma (GBM)" was accepted for the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, and will be presented by David A. Reardon, MD, Professor of Medicine at Harvard Medical School and Clinical Director, Center for Neuro-Oncology at Dana Farber Cancer Institute, on June 1, 2024, in Chicago, IL.

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enLIGHTEN Discovery Platform

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Presented preclinical data at the AACR (Free AACR Whitepaper) Annual Meeting unveiling the second candidate from the enLIGHTEN Discovery Platform, a first-in-class multimodal immunotherapy candidate to induce tertiary lymphoid structures (TLS), being developed as a novel therapeutic for solid tumors.

Anticipated Milestones

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Phase 2 topline OS data for CAN-2409 in NSCLC to be presented at ASCO (Free ASCO Whitepaper) on June 3, 2024
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Updated Phase 1b data (Arm C) for CAN-3110 in rHGG expected in H2 2024
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Phase 2 topline data for CAN-2409 in low-to-intermediate-risk, localized, non-metastatic prostate cancer expected in Q4 2024
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Phase 3 topline disease-free survival data for CAN-2409 in localized intermediate/high-risk prostate cancer expected in Q4 2024

Financial Results for First Quarter Ended March 31, 2024

Research and Development Expenses: Research and development expenses were $4.1 million for the first quarter of 2024 compared to $5.5 million for the first quarter of 2023. The decrease was primarily due to lower employee-related expenses following the corporate restructuring in the fourth quarter of 2023 and lower clinical development costs driven by a reduction in regulatory costs for CAN-2409 programs. Research and development expenses included non-cash stock compensation expense of $0.6 million for the first quarter of 2024 compared to $0.3 million for the first quarter of 2023.

General and Administrative Expenses: General and administrative expenses were $3.8 million for the first quarter of 2024 compared to $4.2 million for the first quarter of 2023. The decrease was primarily due to lower employee-related expenses following the corporate restructuring in the fourth quarter of 2023 and lower insurance costs. These decreases were partially offset by increased professional and consulting fees. General and administrative expenses included non-cash stock compensation expense of $0.5 million for the first quarter of 2024 compared to $0.4 million for the first quarter of 2023.

Net Loss: Net loss for the first quarter of 2024 was $8.2 million, compared to a net loss of $8.8 million for the first quarter of 2023, and included other expense, net of $0.3 million and other income, net $0.8 million, respectively. The change from other income, net in the first quarter of 2023 to other expense, net in the first quarter of 2024 was primarily due to the change in the fair value of the Company’s warrant liability and lower interest income.

Cash Position: Cash and cash equivalents, as of March 31, 2024, were $25.7 million, as compared to $35.4 million as of December 31, 2023. Based on current plans and assumptions, the Company expects that its existing cash and cash equivalents will be sufficient to fund its current operating plan into the fourth quarter of 2024.

On May 14, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported it will share new data from its hematology portfolio and pipeline at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress (EHA2024) in Madrid, Spain, June 13-16, 2024 (Press release, BeiGene, MAY 14, 2024, View Source [SID1234643210]). BeiGene has 28 abstracts accepted at EHA (Free EHA Whitepaper)2024, with four scheduled for oral presentations.

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"As part of our dedication to bringing high-quality therapies to patients around the world, our presentations at EHA (Free EHA Whitepaper)2024 underscore our continued commitment to expanding our hematology portfolio and our efforts to build on the success of BRUKINSA’s unique clinical profile across multiple B-cell malignancies," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "The data highlight the potential of our differentiated investigational BCL2 inhibitor, sonrotoclax, as a monotherapy and in combination regimens, and the promise of BTK degradation to address the unmet needs of patients facing certain blood cancers."

New Data Expand Evidence Base for BRUKINSA (zanubrutinib)

Oral presentation of new data from an arm of the SEQUOIA study in patients with high-risk treatment-naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with del(17p) and/or TP53 mutation treated with BRUKINSA and venetoclax, demonstrating strong efficacy and favorable safety (Abstract S160)
Oral presentation sharing the results of an adverse event (AE) based economic analysis comparing BRUKINSA with acalabrutinib; in terms of AE management, BRUKINSA was cost-saving and associated with quality of life benefits compared to acalabrutinib (Abstract S333)
Presentation of a post hoc analysis evaluating the risk of developing hypertension among ALPINE trial participants with relapsed or refractory (R/R) CLL/SLL, which demonstrated patients in the ibrutinib arm initiated new and/or a new class of anti-hypertensive medications more frequently than patients in the BRUKINSA arm (Abstract P1836)
Results of an intra-patient comparative analysis from ROSEWOOD study of BRUKINSA plus obinutuzumab in patients with R/R follicular lymphoma (FL), supporting the efficacy benefit of the combination in this patient population (Abstract P1143)
Multiple additional presentations featuring patient-reported outcomes and real-world differentiation of BRUKINSA among BTK inhibitors
Emerging Data Demonstrate Hematology Pipeline Strengths

Oral presentation of a Phase 1 study of BeiGene’s novel BCL2 inhibitor sonrotoclax (BGB-11417) in combination with BRUKINSA, demonstrating deep and durable responses with a tolerable safety profile in patients with R/R CLL/SLL; the combination of sonrotoclax with backbone therapy BRUKINSA is being evaluated in the randomized Phase 3 CELESTIAL study (NCT06073821) in patients with TN CLL (Abstract S156)
Poster presentation of Phase 1a/1b open-label dose escalation and expansion study of sonrotoclax in combination with BRUKINSA in R/R mantle cell lymphoma (MCL), showing the combination was generally well tolerated and demonstrated promising efficacy, including high rate of deep and durable responses (Abstract P1112)
Additional presentations highlighting Phase 1 results for sonrotoclax, demonstrating encouraging response rates, durable responses and manageable safety profiles spanning multiple indications across B-cell and myeloid malignancies, including:
As monotherapy in R/R Waldenström’s macroglobulinemia (Abstract P1110)
In combination with azacitidine in both TN and R/R acute myeloid leukemia (Abstracts P538 and P562)
In combination with dexamethasone in R/R multiple myeloma harboring t(11;14) (Abstract P898)
Oral presentation of data from the ongoing, first-in-human Phase 1/2 study of BeiGene’s Bruton tyrosine kinase (BTK) degrader BGB-16673, highlighting tolerable safety and promising efficacy in heavily pretreated patients with R/R CLL/SLL (NCT05006716); BGB-16673, which induces BTK degradation, is the first investigational drug from BeiGene’s chimeric degradation activation compound (CDAC) platform (Abstract S157)
Additional data from the Phase 1/2 study of BTK CDAC BGB-16673, demonstrating a tolerable safety profile and preliminary efficacy in heavily pretreated patients with different types of non-Hodgkin lymphoma, including those with BTKi-resistant disease (Abstract P1119)
BeiGene Presentations During EHA (Free EHA Whitepaper)2024

Abstract Title

Abstract #

Presentation Type

Presenting Author

BTK CDAC (investigational compound)

Preliminary efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed or refractory (R/R) CLL/SLL: Results from the phase 1 BGB-16673-101 study

S157

Oral

R. Parrondo

Preliminary efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed or refractory (R/R) indolent NHL: Results from the phase 1 BGB-16673-101 study

P1119

Poster

C. Cheah

Sonrotoclax (investigational compound)

Results from the phase 1 study of the novel BCL2 inhibitor sonrotoclax (sonro) in combination with zanubrutinib (zanu) for relapsed/refractory (R/R) CLL/SLL show deep and durable responses

S156

Oral

S. Opat

Combination treatment with novel BCL-2 inhibitor sonrotoclax (BGB-11417) and zanubrutinib induces high rate of complete remission for patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL)

P1112

Poster

C. Tam

Safety and efficacy results of a phase 1 study of the novel BCL2 inhibitor sonrotoclax (BGB-11417) for relapsed/refractory Waldenström’s macroglobulinemia

P1110

Poster

C Cheah

Preliminary safety and antileukemic activity of sonrotoclax (BGB-11417), a potent and selective BCL2 inhibitor, in treatment-naive patients with acute myeloid leukemia

P538

Poster

S. Tan

Preliminary safety and antileukemic activity of sonrotoclax (BGB-11417), a potent and selective BCL2 inhibitor, in patients with relapsed/refractory acute myeloid leukemia

P562

Poster

P. Montesinos

Sonrotoclax plus dexamethasone is tolerable and demonstrates antimyeloma activity in patients with relapsed/refractory (R/R) multiple myeloma harboring t(11;14)

P898

Poster

B. Dhakal

BGB-11417-203, an ongoing, phase 2 study of sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, in patients with Waldenström macroglobulinemia

PB2954

Online abstract

J. Matous

CELESTIAL-TN CLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naive (TN) CLL

PB2540

Online abstract

P. Patten

Zanubrutinib

Combination of zanubrutinib + venetoclax for treatment-naive (TN) CLL/SLL with del(17p) and/or TP53: Preliminary results from SEQUOIA arm D

S160

Oral

P. Ghia

Intra-patient comparative analysis of zanubrutinib plus obinutuzumab efficacy in relapsed/refractory follicular lymphoma using the Growth Modulation Index

P1143

Poster

K. Bouabdallah

Risk of hypertension in patients with CLL/SLL who participated in ALPINE: A post hoc analysis

P1836

ePoster

W. White

Risk of new-onset hypertension in newly diagnosed chronic lymphocytic leukemia patients treated with Bruton tyrosine kinase inhibitors: A real-world study using the Symphony Health Solutions database

P1847

ePoster

W. White

Zanubrutinib vs. acalabrutinib in B-cell malignancies: an adverse event-based economic analysis

S333

Oral

T. Munir

Efficacy of zanubrutinib versus acalabrutinib in the treatment of relapsed or refractory chronic lymphocytic leukemia (R/R CLL): A matching-adjusted indirect comparison (MAIC)

P700

Poster

M. Shadman

Efficacy and safety of zanubrutinib vs. venetoclax+ibrutinib in the treatment-naïve (TN) chronic lymphocytic leukemia (CLL): A matching-adjusted indirect comparison (MAIC)

P702

Poster

T. Munir

Matching-adjusted indirect comparison (MAIC) of zanubrutinib versus real-world chemoimmunotherapy (CIT) or chemotherapy (chemo) in relapsed/refractory marginal zone lymphoma (R/R MZL)

P1123

Poster

R. Walewska

Indirect comparison of efficacy of zanubrutinib versus acalabrutinib in the treatment of relapsed/refractory mantle cell lymphoma

P2058

ePoster

B. Shah

Comparative efficacy of Bruton tyrosine kinase inhibitors in the treatment of relapsed/refractory chronic lymphocytic leukemia: A network meta-analysis

P701

Poster

M. Shadman

Zanubrutinib vs other Bruton’s tyrosine kinase inhibitors in relapsed/refractory chronic lymphocytic leukemia: A multilevel network meta-regression

P698

Poster

M. Shadman

Patient-reported outcome (PRO)–based recurrent symptomatic deterioration predicts disease progression: Results from the ALPINE trial

P1834

ePoster

J. Brown

Real-world comparative effectiveness of covalent Bruton tyrosine kinase inhibitors (cBTKi) among patients with relapsed/refractory mantle cell lymphoma (R/R MCL)

P1139

Poster

T. Phillips

Real-world treatment switching and sequencing to next line of therapy of zanubrutinib, acalabrutinib, and ibrutinib in CLL/SLL

P697

Poster

J. Pinilla-Ibarz

Real-world Bruton tyrosine kinase inhibitor treatment patterns and outcomes among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in US community oncology practices

P685

Poster

J. Hou

Real-world evaluation of treatment pattern, time to next treatment, healthcare resource utilization, and cost of care in follicular lymphoma

P1124

Poster

S. Gaballa

Real-world adherence and healthcare resource utilization of Bruton tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma

P2045

ePoster

B. Shah

Recent patterns of care with BTK inhibitors and distribution of social determinants of health among patients with CLL/SLL in the US community setting

PB2546

Online abstract

D. Andorsky

About BRUKINSA (zanubrutinib)

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

About Sonrotoclax (BGB-11417)

Sonrotoclax is an investigational small molecule B-cell lymphoma 2 (BCL2) inhibitor. It belongs to a class of BCL2 homology 3 (BH3) mimetics, and preclinical and IND-enabling studies have demonstrated potent activity and high selectivity of sonrotoclax against the antiapoptotic protein BCL2. Sonrotoclax is more potent and selective for BCL2 relative to BCLxL than venetoclax and shows the potential to overcome common BCL2 resistance mutations.

About BGB-16673

BGB-16673 is an orally available Bruton’s tyrosine kinase (BTK) targeting chimeric degradation activation compound (CDAC) designed to induce degradation of wildtype and multiple mutant forms of BTK, including those that commonly confer resistance to BTK inhibitors in patients who experience progressive disease.

U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib)

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Waldenström’s macroglobulinemia (WM).
Mantle cell lymphoma (MCL) who have received at least one prior therapy.
Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.
The MCL, MZL and FL indications are approved under accelerated approval based on overall response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information including U.S. Patient Information.

This information is intended for a global audience. Product indications vary by region.

On May 14, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, reported financial results for the first quarter ended March 31, 2024 (Press release, Aptose Biosciences, MAY 14, 2024, View Source [SID1234643209]). The Company will provide a corporate update webcast at 5:00 pm ET today, which will include slides focused on the new triplet pilot study expected to deliver clinical data in the second half of this year.

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"Tuspetinib (TUS) has now moved to triplet frontline (1L) treatment for newly diagnosed (ND) acute myeloid leukemia (AML) patients who need a superior 1L therapy. The introduction of venetoclax (VEN) to establish the venetoclax/hypomethylating agent (VEN+HMA) doublet was a major advancement in the frontline treatment of ND AML, but response rates still remain too low and survival too short in 1L therapy. Even more concerning, patients who fail a VEN-containing regimen respond poorly to subsequent salvage therapies in the relapsed or refractory (R/R) setting and have a dismal prognosis," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. "Our solution is the addition of TUS to VEN-HMA to increase response rates, prolong survival, safely improve quality of life, treat a broad spectrum of AML genetic subpopulations, and prevent ND AML patients from becoming resistant to VEN. We’re delighted to have an active protocol to initiate this pilot clinical study and look forward to sharing initial TUS+VEN+HMA triplet data before year-end."

Key Corporate Highlights

Tuspetinib Advancement to TUS+VEN+HMA Triplet Therapy Supported by Extensive Dose Exploration as TUS Single Agent and TUS+VEN Doublet – Tuspetinib, a convenient once daily oral agent that potently targets SYK, FLT3, mutated KIT, JAK1/2, and RSK2 kinases, is being developed for the treatment of patients with ND AML. Tuspetinib avoids many typical toxicities observed with other agents, showing no treatment related QTc prolongation or CPK elevations; no differentiation syndrome; and no drug-related myelosuppression during remission with no drug-related discontinuations or deaths. In the APTIVATE trial, Tuspetinib achieved broad activity across AML patients with a diversity of adverse genetics as a single agent (TUS) and in combination with venetoclax (TUS+VEN) in very ill relapsed/refractory (R/R) and heavily pre-treated AML populations. Blast reductions and responses were observed in patients with Prior-VEN, Prior-FLT3 inhibitor (FLT3i), and Prior-HSCT therapies, those with highly adverse genetics, including mutations in TP53 and RAS genes, and those with mutated or unmutated FLT3 genes. Patients naïve to VEN therapy achieved higher response rates.
Tuspetinib Protocol Now Ready for Triplet Therapy Pilot Study; Clinical Sites Being Activated – Tuspetinib is the ideal third agent for a 1L triplet because of its distinctly favorable safety profile. Tuspetinib enhances antileukemic activity when combined with VEN or HMA in pre-clinical models, Tuspetinib has demonstrated a broad scope of activity across genetic subgroups of AML, and Tuspetinib mechanistically cooperates with VEN to thwart drug resistance. The protocol was submitted to the U.S. Food and Drug Administration (FDA) in Q1, more than 45 days ago, and is currently being activated at clinical sites to initiate the TUS+VEN+AZA triplet pilot study. The new study will enroll ND AML patients who are ineligible to receive intensive induction chemotherapy due to age or co-morbidity. By definition, study participants will be VEN-naïve, FLT3i-naïve, and HMA-naïve, a group that has been shown to be highly responsive to triplet regimens. However, current triplet therapies containing kinase inhibitors can be limited by toxicities often requiring dose reductions of all three agents and are not being pursued in the larger FLT3-unmutated AML population. Clinical sites are now preparing to open the TUS+VEN+HMA triplet study, which is expected to commence enrollment early next quarter. Initial data are expected in the fourth quarter of this year.
Tuspetinib Abstract Accepted for Poster Presentation at EHA (Free EHA Whitepaper) – Aptose will deliver a clinical poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress in Madrid, Spain (Poster ID # P557) that describes the safety and efficacy of tuspetinib (TUS) monotherapy and the TUS+VEN doublet in the APTIVATE Phase 1/2 trial with R/R AML patients. The data illustrate the safety and breadth of activity of TUS and TUS+VEN and support our launch of the TUS+VEN+HMA triplet frontline therapy in newly diagnosed AML. A separate preclinical abstract, which has been accepted for e-poster publication, demonstrates that TUS retains nanomolar potency against AML cells engineered to express the NRAS-G12D mutation or selected for resistance to venetoclax (Poster ID # P1756).
Tuspetinib Preclinical Studies Elucidate Mechanistic Cooperativity Among TUS and VEN – Aptose continues to investigate the mechanisms underlying the complementary activity between TUS and VEN. In addition to targeting certain VEN resistance mechanisms, TUS retains activity against VEN-resistant AML cell lines. Likewise, resistance to TUS creates a synthetic lethality for VEN with a 2000-fold increase in sensitivity to VEN. Other studies demonstrate TUS retains potent antitumor activity in preclinical models of human AML resistant to the gilteritinib FLT3 inhibitor (FLT3i), a finding that is clinically validated by response rates to TUS in R/R AML study participants with prior FLT3i treatment.
Nasdaq – On February 29, 2024, Aptose received a deficiency letter from the Listings Qualifications Department of The Nasdaq Stock Market LLC ("Nasdaq") regarding the previously announced private placement with Hanmi Pharmaceutical, Inc. ("Hanmi") which closed in January 2024. In response to the deficiency letter, Aptose submitted a plan to Nasdaq to regain compliance. On April 25, 2024, the Company received confirmation from Nasdaq that the Company had regained compliance with Nasdaq Listing Rule 5635(d) and determined that the matter is now closed. Pursuant to the Company’s plan to regain compliance, on April 26, 2024, the Company announced that it had amended the terms of the warrant agreement with Hanmi to prohibit the exercise of the warrants if such exercise would result in Hanmi owning more than 19.99% of the issued and outstanding shares of Aptose, unless shareholder approval is first obtained.
On April 2, 2024, Aptose received a second Notification Letter from Nasdaq stating that the Company was not in compliance with Nasdaq’s listing rules because the stockholders’ equity as of December 31, 2023, was below the minimum requirement of $2.5 million. The shareholder’s equity as of December 31, 2023 was negative $2.9 million. As of March 31, 2024, the shareholder’s equity is $137,000, positive. Aptose intends to submit a compliance plan on or before May 17, 2024, to monitor stockholders’ equity and, if appropriate, consider further available options to evidence compliance with the requirement.
Multiple Planned Value-creating Milestones Ahead

TUS and TUS+VEN data in R/R AML to support TUS+VEN+HMA in ND AML: EHA (Free EHA Whitepaper) 2024
Triplet pilot dose initiation planned in ND AML: Summer 2024
Triplet pilot dose escalation planned with early CR/MRD/safety data in ND AML: ASH (Free ASH Whitepaper) 2024
Triplet pilot completed with CR/MRD data and dose selection: EHA (Free EHA Whitepaper) 2025
Triplet Ph2/Ph3 pivotal program planned initiation: 2H 2025

On May 14, 2024 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, reported financial results for the first quarter ended March 31, 2024, and provided a business update (Press release, Aprea, MAY 14, 2024, View Source [SID1234643208]).

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"During the first quarter of 2024, Aprea had a number of noteworthy achievements across clinical, regulatory and corporate fronts," said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. "FDA clearance of the IND for APR-1051, our next-generation inhibitor of WEE1 kinase, was an important milestone and allows us to commence clinical trials with this exciting, differentiated and potentially best in class molecule. We look forward to evaluating its therapeutic activity in patients, focusing on Cyclin E overexpressing cancers, including ovarian and breast cancers amongst others. Enrollment continues in the dose escalation portion of our ABOYA-119 clinical trial evaluating ATRN-119 in patients with advanced solid tumors having mutations in defined DDR-related genes. We are encouraged by correlations of the preliminary signs of clinical benefit and genetic mutations. Importantly, Aprea has a strong balance sheet, and the closing of our successful private placement in March of this year provides us with the capital to fund both our lead programs through meaningful clinical milestones. As we progress, we are committed to leveraging our expertise in synthetic lethality in order to provide hope and new treatment options to cancer patients who urgently need them. We believe that our strategic initiatives and pipeline expansion have the potential to drive substantial value for shareholders."

Key Business Updates and Potential Upcoming Key Milestones

ABOYA-119: ATR inhibitor, ATRN-119, on track to complete monotherapy dose escalation end of the year

ATRN-119 is a potent and highly selective first-in-class macrocyclic ATR inhibitor, designed to be used in patients with mutations in DDR-related genes. Cancers with mutation in DDR-related genes represent a high unmet medical need. Patients with DDR-related gene mutations have poor prognosis and, currently, have no effective therapies.
Enrollment continues in the open-label Phase 1/2a clinical trial of ABOYA-119 (study AR-276-01) as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DDR-related genes.
An update on the ongoing trial was featured in a poster at the AACR (Free AACR Whitepaper) Annual Meeting this past April. As of March 12, 2024, 16 patients were enrolled in the first five cohorts of the dose escalation stage (50 mg/day, 100 mg/daily, 200 mg/daily, 350 mg/daily, and 550 mg/daily). Based on data to date, ATRN-119 has been found to be safe and well tolerated. PK studies show ATRN-119 serum concentrations are entering the expected therapeutic range at the current highest dose level (550 mg). We have clearance up to 800 mg/daily and, on March 12, submitted an amendment to the FDA for the additional cohorts. Preliminary signs of clinical benefit have been observed with two patients achieving stable disease (SD) – one in the 50 mg/day cohort and a second patient who showed longer duration when treated at 200 mg/day. The latter patient at 200 mg/day had SD at Days 55, 112, and 168. For further details, including the status of all 16 patients enrolled to date, refer to the AACR (Free AACR Whitepaper) poster here.
Initial efficacy data from Part 1 of the study may potentially be announced in 2H 2024. At completion of Part 1, the company anticipates identification of a recommended Phase 2 dose (RP2D) that will be used in a Phase 2a cohort expansion (Part 2) to test the tolerability and potential efficacy of ATRN-119 monotherapy in approximately 30 additional patients. The Phase 1 dose escalation is expected to be completed in 4Q 2024, and RP2D is to be determined in 1Q 2025. Enrollment in the Phase 2a cohort is expected to begin in 1Q 2025 with additional efficacy data expected in 3Q 2025.
For more information, please refer to clinicaltrials.gov NCT04905914.
ACESOT-1051: Oral WEE1 inhibitor, APR-1051, expected to enter Phase 1 clinical trial in June, 2024

APR-1051 is a potent and selective small molecule that has been designed to potentially solve liabilities and achieve greater clinical activity than other WEE1 programs currently in development. Aprea is advancing APR-1051 as monotherapy in ovarian and breast cancers with Cyclin E over expression, amongst others. Cancers over expressing Cyclin E represent a high unmet medical need. Patients with Cyclin E over expression have poor prognosis and, currently, have no effective therapies.
In March 2024, the U.S. FDA cleared the Investigational New Drug (IND) application (IND 169359) for APR-1051. Clearance of this IND is allowing Aprea to initiate the Phase 1 ACESOT-1051 trial. This dose escalation trial will evaluate the safety, tolerability, and preliminary efficacy of APR-1051. Enrollment of the first patient is expected in 2Q 2024 with an update expected in 4Q 2024.
APR-1051 was featured in two posters at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting which took place in April 2024 in San Diego, which summarized the pre-clinical data supporting APR-1051 and the trial design for ASECOT-1051.
Pipeline – lead candidate for a third synthetic lethality program to be selected in 2024

Aprea’s research and development team has identified a new target in synthetic lethality. Our chemists and discovery team are developing a series of molecules that are selective and potent against it.
A lead molecule is expected to be declared in 3Q 2024. This program may provide clinically meaningful differences for cancer patients that currently have limited therapies.
An additional poster at AACR (Free AACR Whitepaper) described a combination approach using Aprea’s next-generation macrocyclic ATR inhibitor, ATRN-333, to sensitize glioblastoma (GBM) tumors to lomustine, an oral DNA alkylating agent. The results support further investigation and potential clinical implementation of ATRN-333 and other macrocyclic ATR inhibitors as chemosensitizers for glioblastoma.
Corporate

In March 2024, Aprea announced a securities purchase agreement with new and existing healthcare institutional investors and certain Company insiders to raise up to $34.0 million in gross proceeds, including initial upfront gross funding of $16.0 million and up to an additional $18.0 million upon cash exercise of accompanying warrants at the election of the investors. The financing was led by Sphera Healthcare with participation from new and existing healthcare focused investors including Nantahala Capital, DAFNA Capital Management, Exome Asset Management and Stonepine Capital Management, among others, as well as certain Company insiders. The capital is being deployed for general working capital purposes and to fund the Phase 1 ACESOT-1051 clinical trial, as well as, continuation of patient enrollment in the dose expansion portion of the ABOYA-119 clinical trial evaluating ATRN-119.
Appointed Nadeem Q. Mirza, M.D., M.P.H. as Chief Medical Officer (CMO), effective May 1, 2024. Dr. Mirza had been a consultant to Aprea since February, 2023 and has now assumed a more central role in leading the Company’s development of its expanding clinical pipeline.
Select Financial Results for the First Quarter ended March 31, 2024

As of March 31, 2024, the Company reported cash and cash equivalents of $32.4 million, compared to $21.6 million at December 31, 2023. The Company believes its cash and cash equivalents as of March 31, 2024 will be sufficient to meet its currently projected operating expenses and capital expenditure requirements into the third quarter of 2025.
For the quarter ended March 31, 2024, the Company reported an operating loss of $3.1 million, compared to an operating loss of $4.6 million in the comparable period in 2023.
Research and Development (R&D) expenses were $1.6 million for the quarter ended March 31, 2024, compared to $1.3 million for the comparable period in 2023. The increase in R&D expense was primarily related to IND enabling studies for APR-1051, the Company’s small molecule WEE1 inhibitor, in preparation for enrollment of first patient into Phase 1 dose-escalation in the second quarter of 2024.
General and Administrative (G&A) expenses were $1.9 million for the quarter ended March 31, 2024, compared to $3.4 million for the comparable period in 2023. The decrease in G&A expenses was primarily due to a decrease in personnel costs.
The Company reported a net loss of $2.8 million ($0.67 per basic share) on approximately 4.2 million weighted-average common shares outstanding for the quarter ended March 31, 2024, compared to a net loss of $4.4 million ($1.34 per basic share) on approximately 3.3 million weighted average common shares outstanding for the comparable period in 2023.

On May 14, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported the initiation of an investigator initiated Phase 1 clinical study (NCT06205849) evaluating the safety and efficacy of the company’s lead asset mitazalimab (CD40 mAb agonist) injected intratumorally at the time of surgical irreversible electroporation (IRE) in patients with locally advanced pancreatic cancer (LAPC) (Press release, Alligator Bioscience, MAY 14, 2024, View Source [SID1234643206]).

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The NCI-funded Phase 1a/1b single-center study will enroll up to 18 patients, who will receive a single intratumoral injection of mitazalimab immediately after the surgical IRE, a form of non-thermal ablation that is currently in clinical use for selected patients with LAPC. The study is being conducted by researchers at Moores Cancer Center at UC San Diego. Alligator will supply mitazalimab for the study.

"The preclinical data generated in our lab shows that the combination of IRE with an antibody that stimulates the CD40 receptor improves the response to IRE and inhibits metastatic tumor growth," said Rebekah White, MD, principal investigator of Phase 1 of the study and associate professor of Surgery at UC San Diego School of Medicine. "While IRE is widely used in patients with LAPC, most will ultimately develop distant metastases. We believe that local delivery of mitazalimab at the time of IRE in patients with LAPC will be safe, augment the immune effects of IRE and decrease the risk of recurrence."

"Intratumoral delivery of immunotherapy is gaining increased importance, and in the setting of localized disease provides an opportunity to efficiently activate the immune cells in the tumor microenvironment. In this investigator-initiated study, we are looking forward to evaluating the combination of mitazalimab administered directly into the tumor alongside IRE," said Sumeet Ambarkhane, CMO of Alligator Bioscience. "The strong clinical data generated by mitazalimab over the last 12 months have received a great amount of interest from the scientific and medical communities. We are very pleased that an accomplished center of clinical excellence, such as Moores Cancer Center, is conducting this study, which could broaden the clinical applicability of mitazalimab in pancreatic cancer patients."

In January 2024, Alligator announced positive top-line results from the OPTIMIZE-1 Phase 2 study evaluating mitazalimab in combination with mFOLFIRINOX in 1st line metastatic pancreatic cancer. The study met its primary endpoint and also demonstrated a median Overall Survival (mOS) of 14.3 months, compared to 11.1 months for standard of care, along with an unprecedented Duration of Response of 12.5 months, compared to 5.9 months with FOLFIRINOX alone.