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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 Immatics N.V. (NASDAQ: IMTX, "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported a business update and announced financial results for the quarter ended March 31, 2024 (Press release, Immatics, MAY 14, 2024, View Source [SID1234643224]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our lead cell therapy candidate, IMA203, continues to show deep and durable responses in a significantly expanded data set since our last data readout in November 2023. This update emphasizes the meaningful impact our novel immunotherapy may have on the lives of metastatic cutaneous, uveal and mucosal melanoma patients and the medical needs that IMA203 has a real opportunity to address. We continue to plan to move IMA203 into a registration-enabling clinical trial within this year while also continuing to ramp up our commercial manufacturing buildout," said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. "In addition to IMA203’s progress, we also look forward to presenting the first clinical data on the two lead candidates from our bispecifics pipeline in the second half of the year."

First Quarter 2024 and Subsequent Company Progress

ACTengine Cell Therapy Program

ACTengine IMA203 monotherapy
Today, Immatics is providing a data update on IMA203 monotherapy targeting PRAME from the ongoing Phase 1 trial at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR-T cells) in 30 heavily pretreated metastatic melanoma patients evaluable for efficacy. The treated patient population is composed of patients with a median of 3 lines of prior systemic treatments, consisting of cutaneous melanoma patients (N=17), uveal melanoma patients (N=10), mucosal melanoma patients (N=2) and a patient with melanoma of unknown primary (N=1). The current data represent an update to the previously communicated interim data readout in the IMA203 melanoma efficacy population of November 8, 2023.

As of the data cut-off on April 25, 2024, treatment with IMA203 monotherapy in the efficacy population has demonstrated:

Confirmed objective response rate (cORR) of 55% (16/29)
Disease control rate of 90% (27/30)
Tumor shrinkage in 87% (26/30) of patients
Median duration of response (mDOR) was 13.5 months (min 1.2+, max 21.5+ months) including 11 of 16 confirmed objective responses ongoing at data cut-off and longest duration of response ongoing at >21 months after infusion
Confirmed response rates are similar across all melanoma subtypes (56% (9/16) in cutaneous melanoma; 54% (7/13) in other melanoma subtypes)

To date, IMA203 has maintained a favorable safety profile with no treatment-related grade 5 events in the safety population (N=65 patients across all dose levels and all tumor types).

Best overall response for IMA203 at RP2D in melanoma

More information and details on the IMA203 clinical data update in melanoma are available in the Immatics corporate presentation: View Source

The next data update with translational and clinical data for IMA203 is planned for 2H 2024 at a medical conference.

Immatics’ late-stage clinical cell therapy development is supported by its differentiated manufacturing related to timeline, capabilities and facilities. ACTengine IMA203 cell therapy products are manufactured within 7 days, followed by a 7-day QC release testing at a success rate of >95% to reach the target dose. The company has also recently completed construction of a ~100,000 square foot R&D and GMP manufacturing facility with a modular design for efficient and cost-effective scalability intended to serve early-stage and Phase 2/3 clinical trials, as well as initial commercial supply. The new site will start GMP manufacturing of cell therapy products in early 2025. Meanwhile, the existing GMP facility, which is run in collaboration with UT Health, will remain active until YE 2025 and will also initially serve the Phase 2/3 registrational trial.

Following an RMAT designation in October 2023 and productive interactions with the FDA, Immatics plans to initiate a randomized Phase 2/3 trial in 4Q 2024 for IMA203 in patients with second-line or later (2L+) cutaneous melanoma, potentially also including uveal melanoma patients.

The Phase 2/3 trial is expected to assess IMA203 targeting PRAME in HLA-A*02:01-positive cutaneous melanoma patients versus a control arm. This approach is consistent with the FDA’s "one-trial" approach2, i.e., a single randomized controlled trial to support accelerated approval and the verification of clinical benefit to achieve full approval. The high prevalence of PRAME (≥95%) in cutaneous melanoma may enable the company to enroll patients without PRAME pre-testing. This would enhance trial operations and would remove the need to develop a companion diagnostic for PRAME testing in this indication. The full trial design is currently being developed and is subject to further alignment with the FDA as part of the ongoing discussions. Further details of the final clinical trial design will be provided in 2H 2024.

IMA203 is being developed to treat patients with metastatic melanoma, a prevalent cancer type with increasing incidence both inside and outside the United States. Currently, eligible PRAME-positive melanoma patients for the ongoing trials, i.e., 2L+, HLA-A*02:01 positive, include ~3,000 cutaneous melanoma patients and ~300 eligible uveal melanoma patients3 in the US.

ACTengine IMA203CD8 (GEN2) monotherapy

As of the previously reported interim clinical update from November 8, 2023, the first data on the company’s second-generation product candidate, IMA203CD8 (consisting of PRAME-specific functional CD8+ and CD4+ cells), demonstrated 56% (5/9) cORR with enhanced pharmacology compared to IMA203. mDOR was not reached (min 2.0+ months, max 11.5+ months) at a mFU of 4.8 months. As of the reported September 30, 2023, cut-off date, IMA203CD8 (GEN2) exhibited a manageable tolerability profile.

For IMA203CD8 (GEN2), Immatics cleared dose level 4a (DL4a, up to ~1.6×109 TCR-T cells) in December 2023. Immatics plans to continue dose escalation with the goal to define the optimal dose for further development. In addition to treating melanoma patients, Immatics has also started to expand its clinical footprint outside of melanoma to address a broader patient population with a particular focus on ovarian and uterine cancers.

A next data update for IMA203CD8 (GEN2) is planned for 2H 2024.

TCR Bispecifics Programs

Immatics’ T cell engaging receptor (TCER) candidates are next-generation, half-life extended TCR Bispecific molecules. They are designed to achieve a patient-convenient dosing schedule and to maximize efficacy while minimizing toxicities in patients through the proprietary format using a high-affinity TCR domain against the tumor target and a low-affinity T cell recruiter binding to the T cell.

Upcoming milestones for Immatics’ clinical TCER pipeline
Immatics seeks to deliver clinical proof-of-concept for its novel TCER platform as quickly as possible and plans to provide first clinical data for IMA401 (MAGEA4/8) and IMA402 (PRAME) in 2H 2024.

Key objectives include:

Demonstrating tolerability of the novel, next-generation, half-life extended TCR Bispecifics format;
Optimizing dosing schedule to a less frequent regimen during dose escalation based on pharmacokinetics data;
Demonstrating initial clinical anti-tumor activity (i.e., confirmed objective responses according to RECIST 1.1).

TCER IMA401 (MAGEA4/8)

The Phase 1 dose escalation basket trial to evaluate safety, tolerability and initial anti-tumor activity of TCER IMA401 in patients with recurrent and/or refractory solid tumors is ongoing. IMA401 targets an HLA-A*02:01-presented peptide that occurs identically in two different proteins, MAGEA4 and MAGEA8. This target peptide has been selected based on natural expression in native solid tumors at particularly high target density (peptide copy number per tumor cell identified by Immatics’ proprietary quantitative mass spectrometry engine XPRESIDENT is >5x higher than for a MAGEA4 peptide target used in other clinical trials).

MAGEA4 and MAGEA8 are expressed in multiple solid cancers, including lung cancer, head and neck cancer, melanoma, ovarian cancer, sarcoma and others. Tolerability continues to be manageable with transient low-grade CRS, lymphopenia and neutropenia at high doses, all of which are expected for a bispecific T cell engager. A premedication with low doses of dexamethasone administered prior to the first 4 infusions, as used with other approved bispecific products, has been implemented as a preventative measure for continued dose escalation. Since the implementation of this premedication, to date, no cases of high-grade neutropenia among the patients treated have been observed. Based on pharmacokinetics data, the treatment schedule for IMA401 was switched from weekly to bi-weekly dosing. Confirmed objective responses have been observed in multiple patients.

IMA401 is being developed in collaboration with Bristol Myers Squibb. First clinical data in at least 25 patients in dose escalation across all doses and multiple solid cancers is expected to be announced in 2H 2024.

TCER IMA402 (PRAME)

Immatics initiated the Phase 1/2 trial investigating the company’s fully owned TCER candidate IMA402 in patients with recurrent and/or refractory solid tumors in August 2023 and the first patients have been dosed. Initial focus indications are ovarian cancer, lung cancer, uterine cancer and cutaneous and uveal melanoma, among others. IMA402 targets an HLA-A*02:01-presented peptide derived from the tumor antigen PRAME. This target peptide has been selected based on natural expression in native solid primary tumors and metastases at particularly high target density (peptide copy number per tumor cell identified by Immatics’ proprietary quantitative mass spectrometry engine XPRESIDENT).

Immatics has recently engaged Patheon UK Limited, a subsidiary of ThermoFisher Scientific Inc., for the manufacturing of clinical IMA402 batches for its use within a potential registration-enabling trial. Patient recruitment and dose escalation continue to scale. First clinical data in at least 15 patients in dose escalation across multiple solid cancers, but initially focused on melanoma, is anticipated to be announced in 2H 2024.

Corporate Development

On January 22, 2024, Immatics completed an offering of 18,313,750 ordinary shares at a public offering price of $11.00 per share. The gross proceeds from the offering, before deducting the underwriting discount and offering expenses, were approximately $201.5 million.

First Quarter 2024 Financial Results

Cash Position: Cash and cash equivalents, as well as other financial assets, total €564.0 million ($609.7 million1) as of March 31, 2024, compared to €425.9 million ($460.4 million1) as of December 31, 2023. The increase is mainly due to the public offering in January 2024, partly offset by ongoing research and development activities. The company projects a cash runway into 2027.

Revenue: Total revenue, consisting of revenue from collaboration agreements, was €30.3 million ($32.8 million1) for the three months ended March 31, 2024, compared to €9.8 million ($10.6 million1) for the three months ended March 31, 2023. The increase is mainly the result of the release of the deferred revenue following the termination of the Genmab collaboration.

Research and Development Expenses: R&D expenses were €32.1 million ($34.7 million1) for the three months ended March 31, 2024, compared to €27.6 million ($29.8 million1) for the three months ended March 31, 2023. The increase mainly resulted from costs associated with the advancement of the clinical pipeline candidates.

General and Administrative Expenses: G&A expenses were €11.6 million ($12.5 million1) for the three months ended March 31, 2024, compared to €9.6 million ($10.4 million1) for the three months ended March 31, 2023.

Net Profit and Loss: Net loss was €3.1 million ($3.4 million1) for the three months ended March 31, 2024, compared to a net loss of €19.7 million ($21.3 million1) for the three months ended March 31, 2023. The decrease of net loss resulted mainly from the one-time revenue related to the termination of the Genmab collaboration, as reported previously.

Full financial statements can be found in the 6-K filed with the Securities and Exchange Commission (SEC) on May 14, 2024, and published on the SEC website under www.sec.gov.

Upcoming Investor Conferences

Bank of America Health Care Conference, Las Vegas (NV) – May 14 – 16, 2024
Jefferies Global Healthcare Conference, New York (NY) – June 5 – 7, 2024
To see the full list of events and presentations, visit www.investors.immatics.com/events-presentations.

On May 14, 2024 Nanopharmaceutics, Inc. (OTC:TGRP), a clinical-stage pharmaceutical development company, reported the initiation of a Phase I clinical study with the Robert H. Lurie Comprehensive Cancer Center of Northwestern University "A Phase 1 Adaptive Dose Escalation With Dose Expansion Study of Triapine in Combination With Temozolomide (TMZ) for Patients With Recurrent Glioblastoma" (ClinicalTrials.gov Identifier: NCT06410248) (Press release, Nanopharmaceutics, MAY 14, 2024, View Source [SID1234643268]). The primary objective of this phase 1 study will be to determine the recommended phase 2 dose (RP2D) for Triapine in combination with temozolomide (TMZ). Secondary objectives include evaluation of the safety profile of Triapine in combination with temozolomide (TMZ), progression-free survival (PFS), overall survival (OS), overall response rate (ORR) per RANO criteria, and quality of life per FACT-Br. The study will recruit 40-45 patients with an established diagnosis of recurrent glioblastoma, and there will be an exploratory arm to investigate drug delivery into brain tumor tissue and target engagement in a cohort who are surgical candidates for re-resection of recurrent glioblastoma. Funding for the study is provided by BrainUp.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Oral Triapine has been shown to be safe, tolerable, and convenient in multiple clinical studies. Ribonucleotide Reductase (RNR) Regulatory Subunit 2 (RRM2) targeting with Triapine may overcome chemoresistance and improve the clinical efficacy of TMZ therapy. Preliminary research from Dr. Atique Ahmed’s lab at Northwestern University has uncovered a critical factor that helps glioblastoma, an aggressive brain cancer, resist chemotherapy treatment.

About the Robert H. Lurie Comprehensive Cancer Center of Northwestern University

The Robert H. Lurie Comprehensive Cancer Center of Northwestern University is a National Cancer Institute-designated Comprehensive Cancer Center located on Northwestern Memorial Hospital’s downtown medical campus in the Streeterville neighborhood of Chicago, Illinois, United States.

On May 14, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported the initiation of a Phase II/III trial to evaluate the efficacy of a combination of the HUTCHMED drug candidate surufatinib, the Jiangsu Hengrui Pharmaceuticals Co., Ltd ("Hengrui Pharma") PD-1 antibody camrelizumab, nab-paclitaxel and gemcitabine as a first-line treatment for patients with metastatic pancreatic ductal adenocarcinoma ("PDAC") in China (Press release, Hutchison China MediTech, MAY 14, 2024, View Source [SID1234643170]). PDAC is an exocrine tumor and the most common form of pancreatic cancer. The first patient received the first dose on May 8, 2024.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

PDAC is a highly aggressive form of cancer, representing over 90% of pancreatic cancer cases. Globally, an estimated 511,000 people were diagnosed with pancreatic cancer, leading to approximately 467,000 deaths in 2022, with an average five-year survival rate of less than 10%. In China, an estimated 119,000 people were diagnosed with pancreatic cancer, causing approximately 106,000 deaths in 2022.[1] Treatments such as chemotherapy, surgery and radiation are commonly employed, but have not shown significant improvement in patient outcomes. Under 20% of metastatic pancreatic cancer patients survive more than a year.[ii]

The trial is a multicenter, randomized, open-label, active-controlled, Phase II/III trial to evaluate the efficacy and safety of surufatinib combined with camrelizumab, nab-paclitaxel, and gemcitabine versus nab-paclitaxel plus gemcitabine as a treatment for adults with metastatic pancreatic cancer who have not been previously treated with a systemic anti-tumor therapy. After an initial safety run-in stage, the Phase II/III stage of the study may enroll a further 500 patients, with a primary endpoint of overall survival (OS). Other endpoints include objective response rate (ORR), progression free survival (PFS), disease control rate (DCR), safety, quality of life, duration of response and time to response. Additional details may be found at clinicaltrials.gov, using identifier NCT06361888.

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said, "Emerging data including those from an investigator-initiated study presented at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, demonstrated that combinations of surufatinib, camrelizumab and chemotherapy have promising efficacy in comparison with existing chemotherapy-based treatments in metastatic PDAC.[3] We hope that this partnership will enable us to bring new, potentially life-changing treatment options to patients."

About Surufatinib
Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

Surufatinib is marketed in China by HUTCHMED under the brand name SULANDA, and was first included in the China National Reimbursement Drug List (NRDL) in January 2022 for the treatment of non-pancreatic and pancreatic neuroendocrine tumors (NETs).

About Camrelizumab
Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Currently, more than 10 clinical trials are underway worldwide in a broad range of tumors and treatment settings.

Camrelizumab, under the brand name AiRuiKa, is currently approved for nine indications in China, including hepatocellular carcinoma ("HCC") (second-line and first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma, and nasopharyngeal carcinoma in the first-line setting. All indications have been included in China’s national medical insurance catalog, making it the leading domestic PD-1 product in terms of approved indications and tumor types covered. The U.S. Food and Drug Administration ("FDA") granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021, and accepted a New Drug Application (NDA) for camrelizumab and rivoceranib as a first-line therapy for unresectable HCC, with FDA Prescription Drug User Fee Act (PDUFA) dates in May 2024.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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