On October 7, 2021 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported preclinical data providing further evidence of bezuclastinib as a differentiated, potent, and selective KIT inhibitor (Press release, Cogent Biosciences, OCT 7, 2021, View Source [SID1234590926]). The data were presented in a virtual poster at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper).

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"Today Cogent presented new preclinical data that reinforces bezuclastinib’s selectivity for targeting KIT mutations while demonstrating minimal brain penetration," said Andrew Robbins, President and CEO of Cogent Biosciences. "We are excited with bezuclastinib’s differentiated profile among KIT inhibitors and continue to work quickly to have three clinical trials for AdvSM, NonAdvSM and GIST patients open for enrollment in 2021."

Preclinical studies evaluated the selectivity of bezuclastinib, and other KIT mutant inhibitors, against closely related kinases including PDGFRα, PDGFRβ, and CSF1R. Inhibition of these kinases has been linked to off-target toxicities such as edema and pleural effusions. Comparative screening was performed against a broad spectrum of 71 ion channels, transporters, enzymes, and cell based models, confirming prior evidence that bezuclastinib is a potent and unique inhibitor of KIT A-loop mutations (exon 17/18). In head-to-head studies comparing KIT mutant inhibitors, bezuclastinib demonstrated no activity against closely related kinases, in contrast to other KIT mutant inhibitors with demonstrated potency against PDGFRα and PDGFRβ.

In a nonclinical safety pharmacology study in rodents, bezuclastinib and another KIT A-loop mutant inhibitor were evaluated at doses which closely correlate with clinical exposures previously shown in clinical studies of GIST patients. After three days, bezuclastinib demonstrated minimal brain penetration with a low brain to plasma ratio. These data are supported by a separate neurobehavioral study of bezuclastinib in rodents in which no CNS-related effects were observed. The absence of brain penetration is a preferred feature for a KIT mutant inhibitor as CNS-related adverse events have been observed clinically with some commercially available mutant KIT inhibitors.

Poster Presentation Details for Bezuclastinib:
Title: Preclinical data identifies bezuclastinib as a differentiated KIT inhibitor with unique selectivity to KIT D816V and minimal evidence of brain penetration
Virtual Poster Number: P257
Date/Time: All poster presentations are made available by the conference at the opening of the meeting on October 7, 2021, at 9:00 am ET.

The presentation is available on the Cogent Biosciences website at: View Source

On October 7, 2021 Seagen Inc. (Nasdaq: SGEN) reported that it will report its third quarter 2021 financial results on Thursday, October 28, 2021 after the close of U.S. financial markets. Following the announcement, Company management will host a conference call and webcast that day at 4:30 p.m. Eastern Time to discuss the results and provide a business update. Access to the event can be obtained as follows (Press release, Seagen, OCT 7, 2021, View Source [SID1234590941]):

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Telephone 844-763-8274 (U.S.) or +1 412-717-9224 (international); conference ID 10160629
Webcast with slides can be accessed at investor.seagen.com. A webcast replay will be archived on the Company’s website.

On October 7, 2021 LIPAC Oncology LLC., a pharmaceutical company utilizing its liposome-bound nano-technology platform to provide precision targeted cancer drugs for the treatment of multiple tumor types, reported the U.S. Patent and Trademark Office issued a Notice of Allowance of LIPAC’s U.S. patent application for its next generation, proliposomal paclitaxel compositions formulated for delivery to the bladder and ureter to treat solid tumor carcinomas (Press release, Lipac Oncology, OCT 7, 2021, View Source [SID1234590964]).

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This eventual U.S. patent, with an expected patent term to 2037, is a significant addition to LIPAC’s worldwide patent portfolio, which includes formulation patents granted in the European Union, Japan, China and other countries. LIPAC also has multiple pending patent applications directed to related treatment methods of bladder and ureter solid tumor carcinomas, as well methods of treating intraperitoneal tumors, including ovarian carcinomas.

"This patent allowance recognizes the unique potential of our proliposomal paclitaxel composition to deliver a higher dose of paclitaxel deeper into the urothelial tissue without the systemic toxicity of other paclitaxel formulations," said TR Thirucote, Chairman and Chief Technology Officer of LIPAC Oncology. "We believe the increased potency, penetration and persistence differentiate our composition from existing bladder cancer treatments."

"We are proud of this milestone, which broadens and strengthens our IP portfolio and complements the formulation patents we have already been granted in key geographies around the world," said Will Robberts, President of LIPAC Oncology. "We look forward to advancing our Phase 2b clinical trial of LiPax, our lead investigational candidate for the treatment of low-intermediate risk non-muscle invasive bladder cancer."

About LiPax

LiPax is a precision targeted, locally delivered taxane in Phase 2b development for intravesical instillation in the treatment of non-muscle invasive bladder cancer (NMIBC). Its liposome-bound nano-technology platform achieves targeted tissue penetration with undetectable systemic exposure, toxicity or chemo-related side-effects. NMIBC is the lead program with additional orphan indications in upper tract urothelial cancer (UTUC), thoracic cancers (mesothelioma and malignant pleural effusion) and peritoneal and ovarian cancers. LiPax is designed to enhance the standard of care of outpatient endoscopic tumor removal followed by intravesical instillation using a typical urinary catheter. LIPAC Oncology completed a Phase 2a clinical trial in August 2020 and intends to initiate a Phase 2b study in the second half of 2021 to further investigate LiPax in the treatment of this condition.

On October 7, 2021 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported preclinical data providing further evidence of bezuclastinib as a differentiated, potent, and selective KIT inhibitor (Press release, Cogent Biosciences, OCT 7, 2021, View Source [SID1234590926]). The data were presented in a virtual poster at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper).

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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

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"Today Cogent presented new preclinical data that reinforces bezuclastinib’s selectivity for targeting KIT mutations while demonstrating minimal brain penetration," said Andrew Robbins, President and CEO of Cogent Biosciences. "We are excited with bezuclastinib’s differentiated profile among KIT inhibitors and continue to work quickly to have three clinical trials for AdvSM, NonAdvSM and GIST patients open for enrollment in 2021."

Preclinical studies evaluated the selectivity of bezuclastinib, and other KIT mutant inhibitors, against closely related kinases including PDGFRα, PDGFRβ, and CSF1R. Inhibition of these kinases has been linked to off-target toxicities such as edema and pleural effusions. Comparative screening was performed against a broad spectrum of 71 ion channels, transporters, enzymes, and cell based models, confirming prior evidence that bezuclastinib is a potent and unique inhibitor of KIT A-loop mutations (exon 17/18). In head-to-head studies comparing KIT mutant inhibitors, bezuclastinib demonstrated no activity against closely related kinases, in contrast to other KIT mutant inhibitors with demonstrated potency against PDGFRα and PDGFRβ.

In a nonclinical safety pharmacology study in rodents, bezuclastinib and another KIT A-loop mutant inhibitor were evaluated at doses which closely correlate with clinical exposures previously shown in clinical studies of GIST patients. After three days, bezuclastinib demonstrated minimal brain penetration with a low brain to plasma ratio. These data are supported by a separate neurobehavioral study of bezuclastinib in rodents in which no CNS-related effects were observed. The absence of brain penetration is a preferred feature for a KIT mutant inhibitor as CNS-related adverse events have been observed clinically with some commercially available mutant KIT inhibitors.

Poster Presentation Details for Bezuclastinib:
Title: Preclinical data identifies bezuclastinib as a differentiated KIT inhibitor with unique selectivity to KIT D816V and minimal evidence of brain penetration
Virtual Poster Number: P257
Date/Time: All poster presentations are made available by the conference at the opening of the meeting on October 7, 2021, at 9:00 am ET.

The presentation is available on the Cogent Biosciences website at: View Source

On October 7, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported the initiation of patient enrollment in INNATE tumor-specific expansion cohorts for both JTX-8064 monotherapy and combination therapy of JTX-8064 with its internal PD-1 inhibitor, pimivalimab (Press release, Jounce Therapeutics, OCT 7, 2021, View Source [SID1234590942]). JTX-8064, the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform, is a humanized IgG4 monoclonal antibody designed to specifically bind to the macrophage receptor Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4). By inhibiting LILRB2 binding with its ligands, JTX-8064 reprograms immune-suppressive macrophages to an immune-active state in preclinical studies, potentially enhancing the T cell response and anti-tumor immunity.

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"We are very pleased to announce that we have started dosing patients in the tumor-specific JTX-8064 monotherapy and pimivalimab combination expansion cohorts of our INNATE study," said Beth Trehu, M.D., chief medical officer at Jounce Therapeutics. "We have made enormous progress in INNATE, having advanced the study from initiation of monotherapy dose escalation to the opening of tumor-specific, proof-of-concept, combination expansion cohorts in just nine months. This progress has been driven by the continued dedication of our employees, enthusiasm from investigators and, based on the science, our belief that the mechanism of action of JTX-8064 has the potential to address the major emerging unmet need in immuno-oncology, overcoming PD-(L)1 inhibitor resistance. We look forward to sharing updates on our continued execution of the INNATE study."

Proof-of-concept (POC) expansion cohorts in INNATE will address three different segments of IO patient populations; first, patients whose tumors progressed on or after a prior PD-1 or PD-L1 inhibitor (PD-(L)1i) and whose tumors exhibited primary or acquired resistance; second, IO naïve patients with tumors where no PD-(L)1i treatment is approved; and third, IO naïve patients with tumors that have a PD-(L)1i approval. POC expansion cohorts in INNATE follow a Simon’s two-stage design with the potential to enroll up to 29 patients per combination cohort and 47 patients in the monotherapy cohort if pre-specified criteria are met. If POC is established after evaluation of 29 or 47 patients, respectively, Jounce intends to move JTX-8064 rapidly into registrational trials on a cohort by cohort basis. INNATE will also assess pharmacodynamic and potential predictive biomarkers to guide future development, aligning with Jounce’s philosophy of developing the right immunotherapies for the right patients.

The INNATE trial (NCT04669899) is divided into 4 parts:

Part 1: JTX-8064 monotherapy dose escalation in solid tumors (completed July 2021)
Part 2: JTX-8064 + pimivalimab dose escalation in solid tumors (enrollment completed)
Part 3: JTX-8064 monotherapy expansion cohort in 2nd- to 4th-line PD-(L)1i naïve, platinum-resistant ovarian cancer (initiated August 2021)
Part 4: JTX-8064 + pimivalimab in indication-specific expansion cohorts (initiated October 2021)
Combination expansion cohorts include:
2nd- to 3rd-line non-small cell lung cancer that has progressed on or after a PD-(L)1i
2nd-line+ clear cell renal cell carcinoma that has progressed on or after a PD-(L)1i
2nd- to 4th-line triple-negative breast cancer that has progressed on or after a PD-(L)1i
2nd- to 3rd-line cutaneous squamous cell carcinoma that has progressed on or after a PD-(L)1i
1st-line PD-(L)1i naïve, PD-L1+ head and neck squamous cell carcinoma
2nd- to 4th-line PD-(L)1i naïve, platinum-resistant, ovarian cancer
2nd- to 4th-line PD-(L)1i naïve, undifferentiated pleomorphic sarcoma and liposarcoma
About JTX-8064
JTX-8064 is a humanized IgG4 monoclonal antibody designed to specifically bind to Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting and the 2019 and 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meetings support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical trial named INNATE (NCT04669899) of JTX-8064 as a monotherapy and in combination with Jounce’s internal anti-PD-1 inhibitor, pimivalimab (formerly JTX-4014) is currently enrolling patients with advanced solid tumors into tumor-specific expansion cohorts.

About Pimivalimab
Pimivalimab (formerly JTX-4014) is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Pimivalimab demonstrated a 17% durable overall response rate in a Phase 1 trial of 18 heavily pre-treated PD-(L)1 inhibitor naïve patients, which excluded all tumor types for which PD-(L)1 inhibitors were approved. In this Phase 1 trial, pimivalimab was shown to have an acceptable safety profile. Pimivalimab is currently being assessed in the INNATE Phase 1 trial (NCT04669899) in combination with JTX-8064, a LILRB2 (ILT4) inhibitor. Pimivalimab is also being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab, a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors.