On December 10, 2024 Tasca Therapeutics Corp. ("Tasca"), a biotechnology company leveraging a unique drug discovery platform that identifies and maps novel lipid-binding pockets on proteins to develop new medicines to treat human diseases, reported a $52 million Series A financing, co-led by Regeneron Ventures and Cure Ventures, with participation by Invus Group (Press release, Tasca Therapeutics, DEC 10, 2024, View Source [SID1234649022]). This funding will be used to advance Tasca’s novel drug discovery platform, progress its lead program, CP-383, into Phase 1/2 clinical proof-of-concept studies, and to expand its drug candidate pipeline.

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"We are excited to enter this next phase of company growth with financial support from such leading life science investors and the continued backing of our pioneering scientific co-founders – Xu Wu, Ph.D., David Fisher, M.D., Ph.D., and Duojia Pan, Ph.D.," said Milenko Cicmil, co-founder and chief executive officer of Tasca. "Our first development candidate, CP-383, is a unique first-in-class molecule demonstrating excellent efficacy across multiple cancer types and we are looking forward to progressing it into the clinic."

Named after the Italian word for "pocket," Tasca is harnessing the power of mass spectrometry-based proteomics, coupled with the use of proprietary reagents, to identify proteins that undergo a specific post-translational modification called auto-palmitoylation. The specific sites of auto-palmitoylation, once mapped and characterized, serve as unique binding sites for novel therapeutics that can be developed to modify the function of the target protein. The auto-palmitoylated proteins Tasca identified represent a rich source of druggable targets across a range of therapeutic indications.

Tasca’s most advanced drug candidate, CP-383, is a first-in-class molecule that has demonstrated robust anti-cancer activity in both in vitro and in vivo studies across a broad range of human cancers, and will initially be evaluated in small cell lung cancer, colorectal cancer, head and neck cancer, and brain cancer patients.

Expert Executive Leadership Team

Tasca’s executive leadership team brings decades of experience in drug discovery and development, as well as a successful history of launching and leading new biotechnology programs and start-ups. Tasca’s executives have held major roles at several big pharma companies, including Merck, AstraZeneca, Bristol Myers Squibb, and Novartis. Their deep understanding of oncology matched with drug development and business expertise will enable them to find creative solutions for challenges faced by early-stage biotechnology companies.

"I was immediately impressed by Tasca’s in vivo data, that combined with the amazing leadership that Milenko provides and backing of strong firms like Regeneron Ventures and Cure Ventures," said Praveen Tipirneni, M.D., and chairman of the board. "I look forward to bringing my Morphic Therapeutic experience to the Tasca team."

Added Dave Fallace, co-founder and managing partner at Cure Ventures: "We founded Cure Ventures to help develop curative technologies and Tasca is expanding the boundaries of science with the potential of their platform. The prospect of being able to drug previously undruggable targets in oncology and potentially other indications differentiates Tasca from the competition. We’re confident in their programs and look forward to supporting them as they advance their platform and pipeline."

On December 10, 2024 Tempus, a leader in artificial intelligence and precision medicine, reported four abstracts were accepted for presentation at the 2024 San Antonio Breast Cancer Symposium, which convenes from December 10-13, in San Antonio, Texas (Press release, Tempus, DEC 10, 2024, View Source [SID1234649020]).

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"Presenting our latest research at the San Antonio Breast Cancer Symposium underscores Tempus’ commitment to advancing precision medicine for breast cancer patients," said Ezra Cohen, MD, Chief Medical Officer of Oncology at Tempus. "By leveraging the power of real-world data and AI-driven insights, Tempus is dedicated to empowering clinicians with tools that can improve patient outcomes and accelerate the pace of research in breast cancer."

Highlights of this year’s Tempus presentations include:

Poster Spotlight Presentation (#PS19-02): Economic Impact of Concurrent Tissue and Circulating Tumor DNA Molecular Profiling In Advanced Breast Cancer Patients
Session Date & Time: Thursday, December 12, 2024; 5:30 – 7:00 p.m. CT
Location: Henry B. Gonzalez Convention Center, Hemisfair Ballroom 1-2

Overview: Compared to tissue testing alone, concurrent solid tissue and circulating tumor DNA (ctDNA) testing identified an additional 20% of patients with actionable findings, reducing the need for repeat biopsies and associated adverse events. In a simulated cohort, concurrent testing detected 92 more patients with actionable variants compared to tissue testing alone and prevented 24 additional biopsies at an incremental cost of $2,715 per patient—less than the cost of an extra liquid biopsy. The approach demonstrates an approach for enhancing patient care by improving diagnostic yield and decreasing the number of unnecessary procedures at an incremental cost that is less than the cost of a liquid biopsy.

Poster Presentation (#P1-03-25): Characterization of the tumor immune microenvironment (TIME) and somatic landscape of metaplastic breast cancer (MpBC)
Session Date & Time: Wednesday, December 11, 2024; 12:30 – 2:00 p.m. CT
Location: Henry B. Gonzalez Convention Center, Halls 2 & 3

Overview: A retrospective analysis from the Tempus database revealed that patients with Metaplastic breast cancer (MpBC), a rare, aggressive subtype with a dismal prognosis, had a distinct molecular phenotype compared to non-MpBC. In patients with MpBC, there was a higher prevalence of triple-negative breast cancer (TNBC), and a distinct somatic alteration profile. Somatic alterations in TERT, CDKN2A/B, MTAP and genes involved in the PI3k pathway were more common in MpBC, compared to non-MpBC patients, providing insights into potential therapeutic targets. The study also found a unique tumor immune microenvironment in MpBC, primarily characterized by a higher PD-L1 expression. These analyses provide further rationale to develop new biomarker-selected treatment strategies in a subtype that is challenging to treat and under-represented in trials.

Poster Presentation (#P2-09-21): Low-level Aurora kinase A (AURKA) amplification as a novel personalized biomarker of CDK4/6 inhibitor resistance in patients with hormone-receptor positive (HR+) metastatic breast cancer
Session Date & Time: Wednesday, December 11, 2024; 5:30 – 7:00 p.m. CT
Location: Henry B. Gonzalez Convention Center, Halls 2 & 3

Overview: In a study of patients with HR+/HER2- metastatic breast cancer (HR+ MBC), low-level AURKA copy number gains were found to be common and associated with resistance to CDK4/6 inhibitors (CDK4/6i). The Tempus database was used to analyze genomic records from tumors sequenced with the Tempus xT DNA seq and xR RNA seq assays, revealing that 15% of patients had AURKA amplifications, which are not typically reported by standard sequencing platforms. Findings showed that patients with AURKA amplifications had significantly shorter progression-free survival (9.9 months) on CDK4/6i compared to those without (17 months), suggesting that AURKA amplification is a potential marker of CDK4/6i resistance. This research underscores the importance of identifying low-level AURKA gains, as they could inform more personalized use of emerging AURKA-targeted therapies like alisertib and further studies are needed.

On December 1, 2024 Ensem Therapeutics, Inc. (ENSEM), a pioneering drug discovery and development company that leverages its unique Kinetic Ensemble platform to advance innovative small molecule precision medicines for oncology, reported the first presentation of preclinical data on ETX-636, a potential best-in-class novel allosteric pan-mutant-selective PI3Kα inhibitor and degrader (Press release, ENSEM Therapeutics, DEC 10, 2024, View Source [SID1234649019]). ETX-636 has a differentiated preclinical profile and the potential to deliver clinical benefit to patients with tumors harboring all forms of mutant PI3Kα. The ETX-636 preclinical data is being presented in a poster session during the 47th Annual San Antonio Breast Cancer Symposium ("SABCS") in San Antonio, Texas, on Dec. 12.

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PI3Kα is among the most frequently mutated oncogenes, with activating mutations seen in approximately 16 percent of all tumors and up to 40 percent of hormone receptor positive/HER2-negative advanced breast cancer. However, wildtype PI3Kα is also central to glucose homeostasis and ATP-binding-site orthosteric inhibitors target both mutant and wildtype PI3Kα, resulting in hyperglycemia which limits the clinical utility of these therapeutics.

ETX-636 is a novel orally bioavailable allosteric pan-mutant-selective PI3Kα inhibitor and degrader. This dual mechanism of action results in deep and durable pathway inhibition and induces concordant tumor regression in kinase and helical domain PI3Kα-mutant breast cancer xenografts without inducing wildtype PI3Kα inhibition-mediated hyperglycemia or other toxicities. Additionally, in an ER-positive, HER2-negative, PI3Kα-mutant breast cancer xenograft, ETX-636 is efficacious as a single agent and shows synergistic activity with the standard-of-care agent fulvestrant. ENSEM believes this molecule will significantly improve outcomes for patients with PI3Kα mutations, whether in cancer or rare diseases.

"The promising preclinical results with ETX-636 underscore the potential of our Kinetic Ensemble platform to discover small molecules against high value and difficult to drug targets," said Shengfang Jin, CEO and Co-Founder of ENSEM. "Targeting mutant PI3Kα within tumors while sparing wildtype PI3Kα in normal tissues represents a significant clinical challenge. ETX-636 is a potent mutant-specific allosteric PI3Kα inhibitor and degrader which differentiates it from other compounds in its class." She noted that ETX-636 is completing IND-enabling studies with a first-in-human clinical trial anticipated in the first half of 2025. ENSEM will evaluate ETX-636 as a monotherapy and in combinations with standard-of-care agents in cancer patients harboring PI3Kα mutations.

Poster Details

Title: ETX-636, a Potential Best-In-Class, Oral Small Molecule Allosteric Pan-Mutant-Selective PI3Kα Inhibitor and Degrader
Poster ID: P4-12-18
Sessions: Poster Session 4
Date/Time: Thursday, December 12, 2024, from 5:30 to 7 p.m. CT
Location: Halls 2-3

On December 10, 2024 Scorpion Therapeutics, Inc. ("Scorpion"), a clinical-stage, precision oncology company developing transformational targeted therapies for patients with cancer, reported updated analyses from its Phase 1/2 study of STX-478 in advanced solid tumor patients in a poster spotlight presentation at the San Antonio Breast Cancer Symposium ("SABCS") 2024 and provided program updates, including a new collaboration with Pfizer to evaluate the triplet combination of STX-478 + atirmociclib + fulvestrant in frontline patients with PI3Kα-mutated HR+/HER2- metastatic breast cancer (Press release, Scorpion Therapeutics, DEC 10, 2024, View Source [SID1234649018]).

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"Scorpion is dedicated to expanding the reach of precision medicine to as many patients as quickly as possible. Our updated analyses presented at SABCS show STX-478’s low dose modification rates and increased response rate at higher doses, reflecting its high level of pathway inhibition. These studies, along with our new collaboration with Pfizer to advance the triplet study of STX-478 + fulvestrant with their novel, selective investigative CDK4 inhibitor in frontline patients, bring us one step closer to this ambitious goal," said Adam Friedman, M.D., Ph.D., Chief Executive Officer of Scorpion. "We are committed to being at the forefront of the emerging treatment landscape as we actively enroll our fulvestrant +/- CDK4/6 inhibitors cohorts of STX-478 and explore new triplet combinations with promising next-generation therapies such as atirmociclib."

Expansion Study Collaboration Updates

Scorpion Therapeutics and Pfizer Inc. (NYSE: PFE) entered into a new clinical trial collaboration and supply agreement to evaluate atirmociclib, Pfizer’s investigative selective-CDK4 inhibitor, in combination with STX-478 and fulvestrant in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer in the frontline metastatic setting. Under the terms of the agreement, Scorpion and Pfizer will equally share the development costs of the study. In addition, Pfizer will supply atirmociclib for use in the study and Scorpion will manage the conduct of the study. The STX-478 + atirmociclib + fulvestrant triplet combination is planned to begin in 2H25.

Data from the Phase 1/2 Study of STX-478 in Advanced Solid Tumors at SABCS 2024

Scorpion has shown in Phase 1 monotherapy data that STX-478, an oral, once-daily, mutant-selective, allosteric PI3Kα inhibitor, demonstrated robust PI3Kα pathway inhibition as a monotherapy, with anti-tumor activity observed in multiple cancer types, including a 23% overall response rate (ORR) in HR+/HER2- breast cancer (BC) and a 44% ORR in gynecological tumors, amongst others. STX-478 was well-tolerated, including in pre-diabetic, diabetic and heavily pre-treated patients and showed minimal significant wild-type-mediated toxicities. These results suggest that STX-478 could overcome the limitations of currently available pathway inhibitors and, consequently, meaningfully improve clinical outcomes for patients with PI3Kα kinase or helical domain-mutated solid tumors.

In the poster presented at SABCS 2024, updated analyses for STX-478 demonstrated a favorable safety profile with minimal dose modifications observed, including no patient discontinuations due to an adverse event. Updated efficacy analyses demonstrated a positive dose-response relationship as monotherapy in patients with HR+/HER2- breast cancer, which correlates with a high level of PI3Kα pathway target coverage. Combination cohorts with a STX-478 + fulvestrant doublet and STX-478 + fulvestrant + CDK4/6 inhibitor triplet are actively enrolling in patients with HR+/HER2- breast cancer.

The presentation is available here on Scorpion’s website.

"STX-478 is characterized by a markedly higher therapeutic index, improving clinical outcomes and quality of life for patients during treatment compared to approved non-mutant-selective inhibitors," said Dejan Juric, M.D., Director of the Termeer Center for Targeted Therapies at the Massachusetts General Hospital and STX-478 trial investigator. "Based on the very promising monotherapy results, I look forward to studying STX-478’s activity in doublet and triplet combination trials, particularly those that capture the known synergy between inhibition of PI3Kα and estrogen receptor antagonism in HR+/HER2-breast cancer, as well as CDK inhibition. Development of higher order combinations of increasingly selective targeted therapeutic agents represents the next frontier in precision oncology, and I believe STX-478 is well-positioned to drive major progress in this area."

About STX-478

STX-478 is an allosteric, wild-type-sparing, CNS-penetrant, oral small molecule inhibitor of mutant PI3Kα, a well-known, clinically-validated oncogene associated with a variety of solid tumors and one of the most highly mutated targets in all of cancer, which occurs in more than 166,000 patients per year with breast, gynecological and other solid tumors in the United States alone. Based on preclinical data and initial data from the ongoing Phase 1/2 trial, STX-478 has the potential to address significant unmet needs in patients with PI3Kα-mutant cancers left by existing therapies through less toxicity and sustained and deeper responses. STX-478 is in an ongoing Phase 1/2 trial exploring its activity across a range of solid tumors with both kinase and helical domain mutations. The trial includes patients both previously exposed to and naïve to alpelisib and other PI3K pathway inhibitors and includes expansion cohorts in which STX-478 is being evaluated in combination with fulvestrant in second line HR+/HER2- breast cancer and in combination with fulvestrant plus CDK4/6 inhibitors in frontline HR+/HER2- breast cancer. To learn more about the first-in-human trial of STX-478, please visit this page.

On December 10, 2024 Ensem Therapeutics, Inc. (ENSEM), a pioneering drug discovery and development company that leverages its unique Kinetic Ensemble platform to advance innovative small molecule precision medicines for oncology, reported for the first time preclinical data on ETX-197/BG-68501, a potential best-in-class oral, selective CDK2 inhibitor at the 47th Annual San Antonio Breast Cancer Symposium ("SABCS") in San Antonio, Texas (Press release, ENSEM Therapeutics, DEC 10, 2024, View Source [SID1234649017]). ETX-197/BG-68501 has a differentiated preclinical profile and the potential to deliver clinical benefit to patients with tumors associated with CDK2 dependency.

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CDK2 is a well-established vulnerability of multiple cancers, including tumors with increased expression of Cyclin E (CCNE) or the mutation/loss of the Retinoblastoma 1 gene (RB1). There are currently no approved CDK2 specific drugs. ETX-197/BG-68501 was designed through ENSEM’s Kinetic Ensemble platform to induce previously unexplored interactions within the CDK2 ATP binding pocket, leading to increased potency and selectivity compared to other CDK2 inhibitors.

ETX-197/BG-68501 shows tight binding (slow off-rate) for CDK2 which results in potent and concordant pharmacodynamic modulation and anti-proliferative activity both in vitro and in vivo. ETX-197/BG-68501 is 100-fold more selective for CDK2 over other kinases in the CDK family and this superior selectivity extends more broadly against 385 other kinases, indicating the potential for promising tolerability in the clinic.

In mouse xenograft studies using a CCNE-amplified ovarian cancer cell line or patient-derived tumors, ETX-197/BG-68501 showed sustained target engagement, dose-dependent tumor growth inhibition with excellent tolerability. ETX-197/BG-68501 demonstrated single agent efficacy in a breast cancer xenograft model that had acquired resistance to a CDK4/CDK6 inhibitor. In addition, ETX-197/BG-68501 showed anti-tumor activity in other in vitro and in vivo tumor models including small cell lung and ovarian cancers, indicating its broad clinical potential beyond breast cancer.

"Inhibiting CDK2 potently and selectively over other CDK family members represents a significant challenge," said Shengfang Jin, CEO and Co-Founder of ENSEM. "The promising preclinical results with ETX-197/BG-68501 underscore the potential of our Kinetic Ensemble platform to discover small molecules against high value and difficult to drug targets." She noted that BeiGene is currently conducting a first-in-human Phase 1a/1b clinical study (NCT06257264) to assess the safety tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ETX-197/BG-68501, and is presenting a "Trial-in-Progress" poster for this ETX-197/BG-68501 clinical study at the Symposium.

Poster Details

Title: ETX-197/BG-68501, a potential best-in-class potent, selective oral small molecule CDK2 inhibitor, has anti-tumor activity in cancer models with Cyclin E amplification or deficiency in the Retinoblastoma 1 gene
Poster ID: P4-12-29
Sessions: Poster Session
Date/Time: Thursday, December 12, 2024, from 5:30 to 7 p.m. CT
Location: Halls 2-3