On March 7, 2022 Jounce Therapeutics Presented the Corporate Presentation (Press release, Jounce Therapeutics, MAR 7, 2022, View Source [SID1234609619]).

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On March 7, 2022 Day One Biopharmaceuticals (Nasdaq: DAWN), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported its fourth quarter and full year 2021 financial results and highlighted recent corporate achievements (Press release, Day One, MAR 7, 2022, View Source [SID1234609618]).

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"Our clinical and corporate achievements in 2021 have set a solid foundation for a potentially transformational next 12 months," said Jeremy Bender, Ph.D., chief executive officer of Day One. "We expect to report the initial data from our pivotal Phase 2 FIREFLY-1 trial of DAY101 in relapsed pediatric low-grade glioma in June of 2022 followed by topline results in the first quarter of 2023. In addition, we are enrolling patients in our Phase 2 FIRELIGHT-1 monotherapy trial of DAY101 in RAF-altered solid tumors and are preparing to initiate a Phase 1b/2 combination portion of the study with our oral MEK inhibitor, pimasertib. As our clinical development programs continue to advance and expand, we remain well-capitalized to fund our operations into 2024 and we will continue to execute on our mission to provide innovative targeted therapies for people of all ages."

Program Highlights

•Initial data from FIREFLY-1, a pivotal Phase 2 clinical trial of DAY101 (tovorafenib) in pediatric low-grade glioma (pLGG), is expected in June 2022.

•FIREFLY-1 has reached targeted enrollment across approximately 30 sites globally. Day One anticipates releasing topline results from the study in the first quarter of 2023. Pending positive results from FIREFLY-1, Day One anticipates filing a new drug application (NDA) with the U.S. Food and Drug Administration (FDA) in 2023.

•The first patient has been dosed with a pediatric formulation in the FIREFLY-1 study.

•The Company plans to initiate a pivotal Phase 3 clinical trial (FIREFLY-2) evaluating DAY101 as a first-line therapy in pLGG in the second quarter of 2022.

•Day One is enrolling patients in the Phase 2 FIRELIGHT-1 trial evaluating DAY101 monotherapy in adults with recurrent, progressive, or refractory solid tumors harboring MAPK pathway aberrations, with 8 sites activated. Day One plans to expand FIRELIGHT-1 to include a Phase 1b/2 portion to evaluate DAY101 in combination with pimasertib, the Company’s MEK Inhibitor. The Company expects to initiate the combination portion of the study in March of 2022.

Fourth Quarter and Full Year 2021 Financial Highlights

•Cash Position: Cash and cash equivalents totaled $284.3 million on December 31, 2021. Based on Day One’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into 2024.

•R&D Expenses: Research and development expenses were $11.2 million and $43.6 million for the fourth quarter and full year ended December 31, 2021, respectively, as compared to $4.2 million and $9.1 million for the same periods in 2020. The increase was primarily due to additional employee compensation costs, milestone payments for licensing agreements, clinical trial, and product development expenses.

•G&A Expenses: General and administrative expenses were $10.8 million and $29.2 million for the fourth quarter and full year ended December 31, 2021, respectively, as compared to $2.0 million and $4.7 million for the same periods in 2020. The increase was primarily due to additional employee compensation costs, legal, and professional expenses associated with operating as a public company.

•Net Loss: Net loss totaled $21.9 million for the fourth quarter of 2021 with non-cash stock compensation expense of $5.1 million, compared to $35.6 million for the fourth quarter of 2020 with non-cash stock compensation expense of $0.4 million. Net loss was $72.8 million for the year ended December 31, 2021, with non-cash stock compensation expense of $13.3 million, compared to $43.8 million for the year ended December 31, 2020, with non-cash stock compensation expense of $0.5 million.

Upcoming Events

•Cowen 42nd Annual Health Care Conference
oManagement will participate in a fireside chat today, March 7 at 2:50 p.m. ET. A live and archived audio webcast of the discussion will be available by visiting the Events & Presentations section of the Company’s website.

About DAY101 (tovorafenib)

DAY101 (tovorafenib) is an investigational, oral, brain-penetrant, highly-selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway. Studies have shown DAY101 has high brain distribution and exposure in comparison to other MAPK pathway inhibitors, thus potentially benefiting patients with primary brain tumors or brain metastases of solid tumors. DAY101 is a type II RAF inhibitor found to selectively inhibit both monomeric and dimeric RAF kinase.

DAY101 has been studied in over 250 patients, and as a monotherapy, previously demonstrated good tolerability and encouraging anti-tumor activity in pediatric and adult populations with specific MAPK pathway-alterations. DAY101 has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration who require systemic therapy and who have either progressed following prior treatment or who have no satisfactory alternative treatment options. The FDA has also granted Rare Pediatric Disease Designation to DAY101 for the treatment of low-grade gliomas harboring an activating RAF alteration that disproportionately affects children. In addition, DAY101 has received Orphan Drug designation from the FDA for the treatment of malignant glioma and orphan designation from the European Commission for the treatment of glioma.

DAY101 is being evaluated in a pivotal Phase 2 clinical trial (FIREFLY-1) for the treatment of pediatric low-grade glioma (pLGG). pLGG is the most common form of childhood brain cancer with no approved therapies. Day One has also initiated a Phase 1b/2 study (FIRELIGHT-1) with DAY101 in patients with recurrent or progressive solid tumors with activating RAF alterations and additional studies are planned with DAY101 alone or in combination with other agents that target key signaling nodes in the MAPK pathway, such as the Company’s MEK inhibitor pimasertib, in patient populations where RAS and RAF alterations are believed to play an important role in driving disease.

On March 7, 2022 Nectin Therapeutics Ltd., (Nectin) a biotechnology company developing novel targeted immunotherapies that address resistance to approved immune oncology treatments, and Cancer Focus Fund, LP, a unique investment fund established in collaboration with The University of Texas MD Anderson Cancer Center (MD Anderson) to provide funding and clinical expertise to advance promising cancer therapies, reported a Cancer Focus Fund investment of $5.4 million to finance a Phase 1 clinical trial of Nectin’s PVR blocker, NTX1088, in cancer patients with locally advanced and metastatic solid tumors (Press release, Nectin Therapeutics, MAR 7, 2022, View Source [SID1234609616]).

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NTX1088 is a high affinity monoclonal antibody directed against PVR, an immune checkpoint ligand. NTX1088 blocks the signaling of the immune checkpoint receptors TIGIT and CD96, while restoring the expression and immune function of DNAM1 (CD226), resulting in increased anti-tumor immune effects from activated T cells and natural killer (NK) cells in the tumor microenvironment. PVR is overexpressed in many solid tumors across different cancer indications, including lung, colorectal, liver, ovarian, breast, adrenal, pancreatic, uterine, head and neck, gastric and esophageal. High PVR expression is associated with poor prognosis and with resistance to PD1 blockade, making PVR an attractive therapeutic target for novel immuno-oncology therapies, both as a monotherapy and in combination with PD1 blockers.

The Cancer Focus Fund investment will support a Phase 1 clinical study at MD Anderson, assessing NTX1088 in the treatment of locally advanced and metastatic solid tumors. Cancer Focus Fund is receiving a combination of equity and future payments from Nectin based on achievement of certain clinical and commercial milestones.

"Cancer Focus Fund is committed to advancing the clinical development of novel cancer therapies with the potential to have a significant impact on patients," said Ross Barrett, a founder and Managing Partner of Cancer Focus Fund. "Despite their early promise, the majority of cancer patients do not respond to, or eventually acquire resistance to, current immunotherapies. NTX1088 has a unique mechanism of action that works in three ways to suppress the immune inhibitory effects of tumors while also promoting direct anti-tumor activity. We are delighted to help fund this first-in-human clinical trial at MD Anderson, our collaborator in leading Cancer Focus Fund-financed clinical trials."

The Phase 1 trial is an open label study in 90 patients that will be conducted in two stages – a dose escalation stage and an expansion stage. NTX1088 will be investigated as a single agent and in combination with a PD1 blocker. The primary objectives of the dose escalation stage is to assess safety and tolerability and to select a recommended safe and effective dose. In the expansion stage of the trial, NTX1088’s safety and tolerability will be further evaluated, along with initial efficacy measures and exploratory assessments of pharmacodynamic and predictive biomarkers, which will assist in stratifying patients moving forward. Sarina A. Piha-Paul, MD, an Associate Professor in the Department of Investigational Cancer Therapeutics at MD Anderson, will serve as the Principal Investigator.

"Nectin Therapeutics is developing a portfolio of innovative anticancer compounds directed at highly differentiated targets within the nectin family of immune checkpoints," said Fabian Tenenbaum, Chief Executive Officer of Nectin Therapeutics. "The upcoming initiation of our first-in-human clinical trial is a major milestone for the company. We welcome the financial support from Cancer Focus Fund and clinical expertise of MD Anderson in facilitating the Phase 1 study for this promising new approach to helping patients mount an effective immune response to their cancer."

The Phase 1 trial is expected to begin enrolling patients around mid-year of 2022.

About NTX1088
NTX1088 is a first-in-class monoclonal antibody directed against a key immune checkpoint, PVR, also known as CD155. NTX1088 has a triple mechanism of action. It binds PVR with high affinity and blocks its interactions with TIGIT and CD96, preventing their immune inhibitory signaling. NTX1088 also blocks the interaction between PVR and DNAM1, also known as CD226, a molecule involved in the activation of anti-cancer T cells and NK cells. By preventing internalization and degradation of DNAM1, NTX1088 leads to restoration of DNAM1 expression on the surface of immune cells and results in robust antitumor activity. NTX1088 demonstrated superior antitumor activity compared to approved and investigational immune checkpoint inhibitors in preclinical models and revealed a favorable safety profile in non-human primates.

On March 7, 2022 Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental New Drug Application (sNDA) for TIBSOVO (ivosidenib tablets) as a potential treatment for patients with previously untreated IDH1-mutated acute myeloid leukemia (AML) (Press release, Servier, MAR 7, 2022, View Source [SID1234609615]). The sNDA was granted Priority Review, which accelerates the review and shortens the review time goal from 10 months to 6 months. Priority Review is typically given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists.

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"On the heels of our recent FDA approval of TIBSOVO in cholangiocarcinoma, we are pleased with this important step forward in the agency’s consideration to expand its current indication to include the treatment of patients with previously untreated IDH1-mutated acute myeloid leukemia," said David K. Lee, Chief Executive Officer, Servier Pharmaceuticals. "We are thrilled with the positive momentum of this program as we continue to grow our leadership in oncology and deliver more life-changing medicines to patients living with difficult-to-treat cancers."

The sNDA acceptance is supported by results from the AGILE study, a global, Phase 3 trial in patients with previously untreated IDH1-mutated AML, which were presented at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The data demonstrated that treatment with TIBSOVO in combination with azacitidine significantly improved event-free survival (EFS) (hazard ratio [HR] = 0.33, 95% CI 0.16, 0.69, 1-sided P = 0.0011 1,2). In addition, the combination of TIBSOVO with azacitidine showed a statistically significant improvement in overall survival (OS) (HR = 0.44 [95% CI 0.27, 0.73]; 1-sided P = 0.0005), with a median OS of 24.0 months.

"TIBSOVO is the first therapy targeting cancer metabolism to demonstrate improved event-free survival and overall survival in combination with azacitidine in patients with previously untreated IDH1-mutated AML," said Susan Pandya, M.D., Vice President Clinical Development and Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier Pharmaceuticals. "With this FDA acceptance for Priority Review, we are closer to offering this critical treatment option to patients in the U.S. and we look forward to engaging with regulatory agencies around the world."

TIBSOVO[*] is currently approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory acute myeloid leukemia (AML), and for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. Recently, TIBSOVO was approved as a first and only targeted therapy for patients with previously treated IDH1-mutated cholangiocarcinoma.

In an effort to bring innovative treatment options to patients living with difficult-to-treat cancers, Servier has made oncology a priority globally, and allocates more than 50% of its research and development budget to cancer research. With more than 21 oncology assets at varying stages of clinical development, and 20 research projects ongoing, Servier is committed to finding solutions that address patient needs across the entire spectrum of disease and in a variety of tumor types.

About the NCT03173248 AGILE Phase 3 AML Trial

The AGILE trial is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial designed to evaluate the efficacy and safety of TIBSOVO in combination with azacitidine compared with placebo in combination with azacitidine, in adults with previously untreated IDH1-mutated acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy (≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy). The study’s primary endpoint is EFS, defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure is defined as failure to achieve complete remission (CR) by Week 24.

Key secondary endpoints included CR rate, defined as the proportion of participants who achieve a CR; overall survival (OS), defined as the time from date of randomization to the date of death due to any cause; CR and complete remission with partial hematologic recovery (CRh) rate, defined as the proportion of participants who achieve a CR or CRh; and objective response rate (ORR), defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]), partial remission (PR), and morphologic leukemia-free state (MLFS).

About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults, with approximately 20,000 new cases in the U.S., and 43,000 cases in Europe each year.1,2,7 AML incidence significantly increases with age, and the median age of diagnosis is 68.1 The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML.3 The five-year survival rate is approximately 29.5%.1 For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia.4

On March 7, 2022 Akeso, Inc. (9926.HK) ("Akeso"), a biopharmaceutical company dedicated to the development of innovative antibody drugs, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has approved the IND application for the initiation of the open-label, multicenter phase II trial in China using Cadonilimab (PD-1/CTLA-4 bispecific antibody, AK104) in combination with Docetaxel in patients with advanced NSCLC which progressed on combination therapy of PD-1/L1 inhibitor and platinum-based doublet chemotherapy (Press release, Akeso Biopharma, MAR 7, 2022, View Source [SID1234609614]).

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PD-1/L1 inhibitor plus chemotherapy serves as the first-line treatment for patients with advanced NSCLC. However, more than 70% of patients have progressed one year following the therapy. The current standard treatment for progressive advanced NSCLC is Docetaxel, which the reported progression-free survival (PFS) was approximately 4 months, and overall survival (OS) was approximately 10 months. A new therapeutic approach is needed to improve the prognosis of patients.

Cadonilimab is a bi-specific antibody with dual blockade of both PD-1 and CTLA-4. By combining with Docetaxel, this combo strategy may reduce the risk of delayed efficacy and pseudoprogression and may benefit patients with advanced NSCLC following PD-1/L1 inhibitor and platinum-based doublet chemotherapy.