On August 15, 2024 Ono Pharmaceutical, Co., Ltd. (Headquarters: Osaka, Japan; President: Toichi Takino; "Ono") reported that the U.S. Food and Drug Administration (FDA) accepted a priority review for the New Drug Application (NDA) on August 14 US time for vimseltinib, a colony stimulating factor 1 receptor (CSF1R), for the treatment of patients with tenosynovial giant cell tumor (TGCT), which is under development by Deciphera Pharmaceuticals, Inc. ("Deciphera"), a wholly-owned subsidiary of Ono (Press release, Deciphera Pharmaceuticals, AUG 15, 2024, View Source [SID1234645943]). The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of February 17, 2025. In mid-July, the European Medicines Agency (EMA) accepted a Marketing Authorization Application (MAA) of vimseltinib and has begun the start of the EMA’s centralized review process.

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"Building upon positive results from the MOTION pivotal Phase 3 study and following our recent announcement that EMA review of the vimseltinib MAA has begun, we are excited to initiate the regulatory review process in the US and we look forward to working with the FDA to deliver a new treatment option to patients with TGCT" said Steve Hoerter, President and Chief Executive Officer of Deciphera Pharmaceuticals.

The submission is supported by the data from the pivotal Phase 3 MOTION study, evaluating the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior antiCSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed), compared to placebo. In the study, vimseltinib demonstrated a statistically significant and clinically meaningful objective response rate (ORR) at Week 25 in the intent-to-treat (ITT) population, as assessed by Blinded Independent Radiologic Review (BIRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), versus placebo (40% in vimseltinib arm vs 0% in placebo arm, p <0.0001). Additionally, vimseltinib demonstrated statistically significant and clinically meaningful improvements versus placebo in all key secondary endpoints. The safety profile of vimseltinib is manageable and safety data from MOTION are consistent with data previously disclosed in the Phase 1/2 clinical trial of vimseltinib*. Results from the MOTION study were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and published concurrently in Lancet.

About MOTION Study

The MOTION study is a two-part, randomized, double-blind, placebo-controlled Phase 3 clinical study to assess the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed). The primary endpoint of the study is an objective response rate (ORR) at Week 25 in the intent-to-treat (ITT) population, as assessed by Blinded Independent Radiologic Review (BIRR) per using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), versus placebo. The secondary endpoint includes ORR per tumor volume score (TVS), active range of motion (ROM), physical function, stiffness, quality of life, and pain, all assessed at Week 25. This study consists of two Parts. In Part 1, patients were randomized to receive either vimseltinib or placebo for 24 weeks. In Part 2, patients randomized to placebo in Part 1 have the option to receive vimseltinib, and all patients receive vimseltinib for a long-term period in an open-label setting.

About Tenosynovial Giant Cell Tumor (TGCT)

TGCT is a rare disease caused by a translocation in colony-stimulating factor 1 (CSF1) gene resulting in overexpression of CSF1 and recruitment of colony-stimulating factor 1 receptor (CSF1R)-positive inflammatory cells into the lesion. TGCT is a rare, non-malignant tumor that develops inside or near joints. TGCT is caused by dysregulation of the CSF1 gene leading to overproduction of CSF1. TGCT is also known as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS), a diffuse-type of TGCT. Although benign, these tumors can grow and cause damage to surrounding tissues and structures inducing pain, swelling, and limitation of movement of the joint. Surgery is the main treatment option; however, these tumors tend to recur, particularly in diffuse-type TGCT. If untreated or if the tumor continually recurs, damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability. For a subset of patients who are not amenable to surgery, systemic treatment options are limited and a new therapeutic option for TGCT is needed.

About Vimseltinib

Vimseltinib is an investigational, oral switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. Vimseltinib has been developed using Deciphera’s proprietary switch-control kinase inhibitor platform.

On August 15, 2024 LIXTE Biotechnology Holdings, Inc. ("LIXTE" or the "Company") (Nasdaq: LIXT and LIXTW), a clinical stage pharmaceutical company, reported it will be presenting at two investor conferences (Press release, Lixte Biotechnology, AUG 15, 2024, View Source [SID1234645984]):

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■ The Investor Summit Summer 2024 Virtual Conference Tuesday, August 20, 2024, at 2 p.m. EDT/11 a.m. PDT. To access the presentation, visit LIXTE’s investor relations website at View Source

■ The H.C. Wainwright 26th Annual Global Investor Conference, on demand starting at 7 a.m. EDT/4 a.m. PDT, September 9-11, 2024. To access the virtual presentation, register for the conference at www.hcwevents.com/annualconference.

Bas van der Baan, CEO of LIXTE, will present an overview of the Company’s clinical trials with LB-100, its proprietary compound focused on enhancing chemotherapy and immunotherapy treatments as cancer therapies. Proof-of-concept clinical trials are currently in progress for colorectal, ovarian and sarcoma cancers, including trials funded by GSK and Roche.

On August 15, 2024 Pathos AI, Inc. (www.pathos.com), a biotechnology company focused on revolutionizing precision medicine in cancer by harnessing the power of machine learning to transform drug development, reported the world-wide license of PRT811, a potent, selective, and orally bioavailable brain penetrant SAM-competitive PRMT5 inhibitor from Prelude Therapeutics (Press release, Pathos AI, AUG 15, 2024, View Source [SID1234653830]).

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PRT811 (renamed P-500) was developed by Prelude Therapeutics and completed a Phase 1 trial in March 2023. The trial enrolled patients with solid tumors including high-grade glioma and uveal melanoma and has potential application in other indications with high unmet need. Out of 16 patients with high-grade glioma with isocitrate dehydrogenase mutations (IDH+) in the Phase 1 trial, two confirmed complete responses (CR) were observed. At last follow-up, 1 response is ongoing and has lasted 31.0 months while the duration of response for the second CR patient was 7.5 months. Additionally, 1 patient achieved an unconfirmed partial response (PR).

In addition, out of 23 uveal melanoma patients (10 patients with splicing factor 3B subunit 1 (SF3B1) splicing mutations and 13 without an SF3B1 mutation), one confirmed PR (duration of response of 10 months) and a second unconfirmed PR were observed, both in patients SF3B1 mutations.

In the entire safety population (N=86), the most common adverse events of any grade, with an incidence of >20% were nausea (60.5%), vomiting (46.5%) fatigue (36.0%), constipation (29.1%), and thrombocytopenia (24.4%), and were predominantly grade 1-2. The most common adverse events (grade ≥3), occurring >5% were thrombocytopenia (9.3%), anemia (9.3%), and fatigue (5.8%).

"These results from Prelude’s Phase 1 study are promising news for high-grade glioma patients and clinicians, who still have limited treatment options with chemotherapy and radiation that hasn’t changed in decades. With our AI Platform, we aim to increase the already encouraging response rate of P-500 through a novel biomarker-driven strategy, ultimately bringing this medicine to patients as efficiently as possible," said Ryan Fukushima, Pathos CEO.

"Prelude’s discovery engine has delivered a number of first- or best-in-class precision medicines including PRT811, a molecule that has shown early promise in the treatment of high-grade glioma. We are confident that Pathos AI, sharing our passion for precision medicine and commitment to serving cancer patients with high unmet need, is an ideal company to drive the development of this molecule forward for patients." said Sean Brusky, Prelude CBO. "The resources from this transaction will support advancing Prelude’s pipeline."

About P-500
P-500 (previously PRT811) is a selective, brain-penetrant small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5) that has the potential to provide clinical benefit for patients with advanced solid tumors, including high-grade glioma and uveal melanoma.

PRMT5 is an enzyme that adds methyl groups to proteins in cells using a molecule called S-adenosylmethionine (SAM) which regulates protein function and interactions. Several processes that support cancer cell growth and spread depend on PRMT5, making P-500 relevant not only to advanced high-grade glioma and uveal melanoma (in which objective responses to P-500 were observed in the Phase 1 clinical trial) but also to a number of other cancer indications. Preclinical studies have demonstrated PRMT5 inhibition can sensitize cancer cells to other treatments, expanding the application of P-500 to combination therapy in additional indications.

On August 15, 2024 Exscientia reported recent advancements in the Company’s pipeline, collaborations and operations, as well as financial results for the second quarter and first half 2024 (Press release, Exscientia, AUG 15, 2024, View Source [SID1234645944]).

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"Last week, we announced that Exscientia entered into a definitive agreement to combine with Recursion Pharmaceuticals," said David Hallett, Ph.D., interim Chief Executive Officer and Chief Scientific Officer of Exscientia. "When we bring together our platforms at closing, our world class scientists and Exscientia’s best-in-class focused precision oncology internal pipeline with Recursion’s first-in-class focused pipeline, we believe we will be able to discover better drugs for patients faster and at a lower cost."

"In the first half of 2024, we believe we have made important progress across our AI-powered pipeline and progress towards autonomous drug design as well as deepening our technology and pharma partnerships," continued David Hallett, Ph.D. "We made the strategic decision to fully invest in our CDK7 inhibitor GTAEXS617 (‘617) by acquiring full rights to the programme, which we believe is highly differentiated and demonstrates the power of our design capabilities. We look forward to sharing topline data later this year."

Key Business Updates

Transaction with Recursion
●Earlier this month, Exscientia entered into a definitive agreement to combine with Recursion Pharmaceuticals in a transaction that will create a company positioned to leverage the latest life sciences and technology advances to deliver better, novel treatments to patients, faster and at a lower cost relative to traditional drug discovery and development methods
oThis combination will bring together Recursion’s scaled biology exploration and translational capabilities with Exscientia’s precision chemistry design and small molecule automated synthesis capabilities to create, at closing, a leading technology-first, end-to-end drug discovery platform

Internal Precision Oncology Pipeline
●The Company continues to enrol patients with advanced solid tumours in its Phase 1/2 ELUCIDATE trial evaluating ‘617, a potential best-in-class CDK7 inhibitor
○In July, the Company announced that it reached an agreement to acquire the full rights to ‘617 from its partner GT Apeiron – with GT Apeiron retaining an interest via an increased ownership stake in Exscientia
○The Company remains on track to announce topline pharmacokinetic, pharmacodynamic and safety data from the dose escalation phase of ELUCIDATE in the second half of this year
○Exscientia expects to transition to the dose expansion phase of ELUCIDATE in the second half of this year or early next year, starting with the evaluation of ‘617 in HR+/HER2- breast cancer in combination with a selective estrogen receptor degrader (SERD)
●EXS74539 (‘539), Exscientia’s highly differentiated, brain penetrant LSD1 inhibitor, continues to advance towards the clinic, with an IND expected to be submitted later this year. The Company expects to initiate a Phase 1/2 clinical trial in early 2025
●Exscientia remains on track to submit a CTA for EXS73565 (‘565), the Company’s potential best-in-class MALT1 inhibitor, in the second half of 2024. The Company expects to initiate a Phase 1/2 clinical trial of ‘565 in B-cell malignancies, including chronic lymphocytic leukaemia (CLL), in early 2025

Collaborations & Partnerships
●The Sanofi partnership, with a primary focus on immunology and inflammation, continues to advance with multiple potential near-term milestones
●Exscientia continues to make progress in its collaboration with Merck KGaA, Darmstadt, Germany with multiple programmes already in early discovery
●In July 2024 the Company announced a collaboration with READDI, a non-profit biotechnology initiative funded by the National Institute of Allergy and Infectious Disease (NIAID), to evaluate and improve a range of AI-designed antiviral compounds for pandemic preparedness
○Exscientia will use its generative AI capabilities to design novel compounds to fight coronaviruses with READDI providing antiviral expertise as well as funding testing and analyses

Drug Discovery Platform
●Exscientia announced the expansion of its work with Amazon Web Services (AWS) to use the cloud provider’s artificial intelligence and machine learning services to power its platform for end-to-end drug discovery and automation
oExscientia’s state-of-the-art platform, built using AWS technologies, integrates generative AI drug design and robotic lab automation to further accelerate drug development at a lower cost
oThe Company’s closed loop "Design-Make-Test-Learn" facility is now fully online and the first compounds have rolled off the production line. These were designed using Exscientia’s proprietary synthesis aware GenAI and manufactured and tested using the Company’s in-house state-of-the-art automation facility

Leadership Updates
●Marie-Louise Fjallskog, M.D., Ph.D., was appointed interim Chief Medical Officer, bringing extensive oncology drug development expertise to execute robust clinical strategy on Exscientia’s internal oncology pipeline
●Nicola Richmond, Ph.D., will be joining Exscientia in September as Chief Scientist, AI. Holding a Ph.D. in mathematics, she brings over 20 years’ experience operating at the intersection of drug discovery and technology. Dr. Richmond will be leading efforts in developing AI solutions for the Company’s drug discovery efforts

Second Quarter and First Half 2024 Financial Results
For the convenience of the reader, the Company has translated pound sterling amounts to U.S. dollars at the rate of £1.000 to $1.2640, which was the noon buying rate of the Federal Reserve Bank of New York on June 28, 2024.

Revenue: Revenue for the three and six months ended June 30, 2024 was $5.6 million and $12.3 million, compared to $3.8 million and $11.1 million for the three and six months ended June 30 2023. The increase in revenue year over year was primarily due to an increase in the number of active projects in the first half of 2024 relative to the prior period.

Research and development expenses (R&D): R&D expenses for the three and six months ended June 30, 2024 were $31.7 million and $61.5 million respectively, as compared to $41.7 million and $83.9 million for the same period ended June 30, 2023. The decrease in research and development expenses was primarily due to cost reductions relating to pipeline prioritisation activities implemented during the second half of 2023 and cost savings from operational efficiencies.

General and administrative expenses (G&A): G&A expenses for the three and six months ended June 30, 2024 were $21.2 million and $25.6 million, respectively, or 34% and 24% of total operating expenses. For the three months ended June 30, 2024, G&A expenses increased by $6.5 million compared to the prior year, primarily driven by current quarter severance and termination-related costs totalling $7.5m relating to the cost saving and efficiency measures announced in May 2024. For the six months ended June 30, 2024, G&A expenses decreased by $2.9 million compared to the prior year due to credits totalling $7.5 million relating to amounts recognised in February 2024 on the forfeiture of share options held by the Company’s prior CEO upon his exit from the Company.

Cash inflows: For the second quarter 2024, Exscientia received $1.4 million in cash inflows from its collaborations as compared to $0.7 million during the second quarter 2023.

Net operating cash flow and cash balance: For the three and six months ended June 30, 2024, net operating cash outflows were $45.8 million and $84.8 million respectively, in comparison to $52.2 million and $107.0 million for the three and six months ended June 30, 2023. Cash, cash equivalents and short-term bank deposits as of June 30, 2024 were $370.1 million, as compared to $458.9 million as of December 31, 2023 using the June 28, 2024 constant currency rate.

On August 15, 2024 NuCana plc (NASDAQ: NCNA) reported financial results for the second quarter ended June 30, 2024 and provided an update on its broad clinical development program with its transformative ProTide therapeutics (Press release, Nucana BioPharmaceuticals, AUG 15, 2024, View Source [SID1234645945]).

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As of June 30, 2024, NuCana had cash and cash equivalents of £11.6 million compared to £12.9 million as of March 31, 2024 and £17.2 million at December 31, 2023. NuCana continues to advance its numerous clinical programs and reported a net loss of £7.0 million for the quarter ended June 30, 2024, as compared to a net loss of £5.4 million for the quarter ended June 30, 2023. Basic and diluted loss per ordinary share was £0.12 for the quarter ended June 30, 2024, as compared to £0.10 per ordinary share for the comparable quarter ended June 30, 2023.

"During the first half of the year, we remained focused on the execution of our clinical programs, all of which are on track for data updates this year," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "NUC-3373, a ProTide transformation of 5-FU, is currently being evaluated in three clinical studies: NuTide:323, a randomized, 182-patient Phase 2 study for the second-line treatment of patients with metastatic colorectal cancer; NuTide:302, a Phase 1/2 study in patients with metastatic colorectal cancer; and NuTide:303, a Phase 1b/2 study in patients with solid tumors and lung cancer. We are pleased to report that all three studies are progressing as planned, and we look forward to sharing data updates in the second half of 2024."

Mr. Griffith continued: "In addition, NUC-7738, a ProTide transformation of a novel nucleoside analog, 3’-deoxyadenosine, is being assessed in the Phase 2 part of the ongoing Phase 1/2 NuTide:701 study in PD-1 inhibitor-resistant melanoma patients. Following a positive data update at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting earlier this year, we plan to announce additional data at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024, being held September 13-17 in Barcelona, Spain."

Mr. Griffith concluded, "Our commitment to improving treatment outcomes for patients with cancer is what drives us to advance our development programs. We expect to announce numerous important data readouts in the second half of this year and look forward to providing updates on our progress."

2024 Anticipated Milestones

NUC-3373 (a ProTide transformation of 5-FU)

In 2024, NuCana expects to:

Announce data from the randomized Phase 2 (NuTide:323) study of NUFIRI + bevacizumab compared to the standard of care FOLFIRI + bevacizumab for the second-line treatment of patients with metastatic colorectal cancer;
Announce data from the Phase 1b/2 (NuTide:302) study of NUFIRI + bevacizumab and NUFOX + bevacizumab for the second-line treatment of patients with metastatic colorectal cancer; and
Announce data from the Phase 1b/2 (NuTide:303) modular study of NUC-3373 in combination with pembrolizumab in patients with solid tumors and in combination with docetaxel in patients with lung cancer.
NUC-7738 (a ProTide transformation of 3’-deoxyadenosine)

In 2024, NuCana expects to:

Announce data from the Phase 2 part of the Phase 1/2 study (NuTide:701) of NUC-7738 in combination with pembrolizumab in patients with melanoma.