On October 8, 2021 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of MasterKey therapies, reported the presentation of preclinical data for three early-stage pipeline programs in oral and poster sessions at the 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) (Press release, Black Diamond Therapeutics, OCT 8, 2021, View Source [SID1234591032]).

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"Despite clinical advances in precision medicines for patients with non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, multiple areas of unmet need persist, which include patients whose tumors have developed resistance to current-generation therapies, express non-canonical (or uncommon) mutations, and have metastasized to the brain," said Elizabeth Buck, Ph.D., Chief Scientific Officer of Black Diamond Therapeutics. "BDTX-1535 has demonstrated a breadth of coverage of oncogenic EGFR mutations expressed in NSCLC, which coupled with a brain-penetrant pharmacokinetic (PK) profile, supports the potential of BDTX-1535 as an optimal therapeutic candidate for these NSCLC patient populations."

Dr. Buck continued: "Additionally, B-Raf (BRAF) and fibroblast growth factor receptor (FGFR) are validated therapeutic targets, yet current standards of care are associated with meaningful limitations, yielding persistent unmet needs for these cancer patients. Our BRAF program compounds are designed to selectively target a full spectrum of Class II/III BRAF oncogenic mutations without inducing paradoxical activation, which can lead to secondary malignancies. Our FGFR compounds are designed to target a full spectrum of oncogenic FGFR2 and FGFR3 mutations, including known resistance mutations, while sparing FGFR1, the inhibition of which is associated with toxicities, including hyperphosphatemia."

The presentations describe the following data:

BDTX-1535 Program:
The presentation describes preclinical data for BDTX-1535, which is designed as a potent, selective, and brain-penetrant inhibitor of a spectrum of EGFR mutations expressed in glioblastoma multiforme (GBM) and NSCLC.

In cell-based assays, BDTX-1535 achieved potent and selective inhibition of EGFR mutations expressed in NSCLC, including the EGFR- C797S mutation that can arise following treatment with osimertinib.
BDTX-1535 demonstrated a favorable brain-penetrant PK profile in mouse, rat, and dog models.
In an EGFR Exon19+C797S mouse allograft efficacy model, BDTX-1535 showed dose-dependent tumor growth inhibition and achieved complete regression without notable impact on body weight.
Black Diamond expects to file an Investigational New Drug (IND) application for BDTX-1535 in the first half of 2022.
BRAF Program:
The presentation describes preclinical data for a lead compound from Black Diamond’s BRAF program, which is designed for potency and selectivity against a spectrum of non-canonical Class II/III (non-V600) mutations, as well as to avoid induction of paradoxical activation.

In cell-based assays, the lead compound demonstrated potent inhibition of a spectrum of Class II/III BRAF mutations.
In contrast to current-generation BRAF inhibitors, such as encorafenib and vemurafenib, treatment of cells harboring wild type BRAF (WT-BRAF) with the Black Diamond compound was not observed to lead to an increase in protein kinase RNA-like endoplasmic reticulum kinase (pERK), a signal of paradoxical activation.
In a BRAF-KIAA1549 fusion allograft tumor model, the lead compound exhibited dose-dependent inhibition of pERK and anti-tumor efficacy.
Black Diamond anticipates an IND filing in 2022.
FGFR Program:
The presentation illustrates the Black Diamond approach, which centers on a four-pronged optimization strategy designed to deliver an inhibitor with broad coverage of FGFR2 and FGFR3 oncogenes, while sparing inhibition of FGFR1 and retaining activity against resistance mutations.

In cell-based assays, FGFR program compounds demonstrated potent and selective inhibition of a spectrum of FGFR2/3 oncogenic mutations, while sparing FGFR1.
Additionally, in cell-based assays, FGFR program compounds demonstrated improved potency against resistance mutations.
In an in vivo study conducted in a UM-UC-14 (FGFR3-S249C) mouse model, FGFR program compounds demonstrated anti-tumor activity. Additionally, in mouse and rat models, FGFR program compounds did not promote hyperphosphatemia.
Black Diamond anticipates an IND filing in 2022.
"Our BDTX-1535, BRAF, and FGFR programs exemplify Black Diamond’s MasterKey approach to drug discovery in which we are able to harness the power of our proprietary MAP drug discovery engine to design spectrum-selective candidates engineered to overcome the limitations of current therapies in each target area," said David M. Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "These programs underscore the productivity of our MAP engine, and we look forward to providing updates across our pipeline as we advance toward our goal of delivering product candidates that can expand the reach of precision medicine and, in turn, address areas of true unmet need."

The presentations from the AACR (Free AACR Whitepaper)-NCI-EORTC meeting are available on the "Scientific Presentations and Publications" section of the Black Diamond Therapeutics website.

On October 8, 2021 Pacific Cancer Care and Deep Lens reported that they are collaborating to optimize clinical trial matching and accelerate enrollment at the Monterey-based practice through the use of Deep Lens’ artificial-intelligence (AI) based solutions and other services (Press release, Pacific Cancer Care, OCT 8, 2021, View Source [SID1234591026]). Pacific Cancer Care is the largest hematology and oncology practice on the California Central Coast. Deep Lens is a digital healthcare company that helps community oncology practices improve and expand clinical research programs through the use of their proprietary AI solution, VIPER. This partnership will expand Pacific Cancer Care’s existing clinical trial offering to patients by more accurately and effectively identifying eligible patients for trials, improving communications between patient care teams and bringing more trials to the practice.

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"Clinicals trials are not only critical to the advancement of new therapeutic options for cancer, but they present a unique opportunity for patients to access novel treatments well in advance of their commercialization, some of which may help positively impact the state of their disease," said Zach Koontz, M.D., oncologist at Pacific Cancer Care. "We are excited to partner with Deep Lens to broaden our clinical research program through an increased number of trials that we can offer onsite and by expediting the time we can get patients into these trials. We have a very busy practice and we look forward to leveraging other Deep Lens services to help alleviate some of the administrative tasks associated with clinical trial recruitment, so that our staff can focus more exclusively on patient care."

It is estimated that more than 15,000 oncology clinical trials are actively recruiting patients; however, fewer than 1 in 30 patients participate in a clinical trial. Limited trial site resources make it time-consuming to identify eligible patients, especially as trial protocols increase in complexity. VIPER supports care teams by automating the identification of potentially eligible patients at the time of diagnosis and easily matching them to relevant trials.

"Pacific Cancer Care already has an extremely comprehensive clinical research program – they’ve been the first site to offer access to certain therapies via clinical trials and they place great importance on the role that clinical research plays in the overall acceleration of our knowledge and treatment of cancer," said Simon Arkell, president and co-founder at Deep Lens. "We are thrilled to align with such a prominent, reputable practice that is just as passionate as Deep Lens about innovation and the potential of precision therapies for the treatment of cancer. We look forward to helping this practice better serve the Central Coast oncology community."

Deep Lens’ VIPER will pre-screen all patients from Pacific Cancer Care’s EMR (OncoEMR) and integrate molecular data feeds from Caris Life Sciences, Foundation Medicine and Guardant Health as well as all pathology feeds to automatically identify qualified patients for clinical trials. Deep Lens pre-screening and clinical trial matching solution is provided at no cost to oncology practices.

Deep Lens is working with a significant number of community oncology practices representing every region in the U.S. It is estimated that approximately 85 percent of cancer patients are diagnosed and treated at local, community-based oncology practices. Deep Lens is committed to expanding important oncology research by making trials more accessible to a larger and more diverse population within these local community settings.

On October 8, 2021 Compass Therapeutics, Inc. (OTC:CMPX) and ABL Bio (KOSDAQ: 298380) reported that clinical trial data for CTX-009 (ABL001/ES104), a dual anti-angiogenic bispecific antibody targeting DLL4 and VEGF-A, at an oral plenary session during the AACR (Free AACR Whitepaper)-NCI-EORTC 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) (Abstract Number: 4749; Session Title: Plenary Session 2: New Drugs on the Horizon I) (Press release, Compass Therapeutics, OCT 8, 2021, View Source [SID1234591025]).

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The first in human Phase 1 single agent dose escalation and expansion study evaluated CTX-009 across nine dose levels. The study enrolled 45 heavily pre-treated patients with cancers primarily of colorectal and gastric origin. CTX-009 was well tolerated across all doses evaluated, with no dose-limiting toxicities reported. The most frequent treatment related adverse event was hypertension, observed in 17 patients of the 45 patients enrolled. Among those, 7 patients reported Grade 3 hypertension and the rest had Grade 1 or Grade 2 (16%). Only 4 mild cases of pulmonary hypertension were reported that were all reversible, and CTX-009 demonstrated significant clinical activity as a stand-alone therapy. The majority (87%) of the patients enrolled in the study had ECOG performance status of 1; 42% (n=19) were patients with gastric cancer and 40% (n=18) were patients with colorectal cancer with a median of three prior lines of systemic anticancer therapies. Importantly, 62% of the patients enrolled were previously treated with anti-VEGF antibodies containing regimens. There were 4 partial responses (including three partial responses confirmed by RECIST 1.1 and one partial response which was unconfirmed) and 20 stable diseases among 39 evaluable patients. The confirmed overall response rate (ORR) across all dose levels tested (0.3 – 17.5mg/kg) was 8%, not including 1 unconfirmed partial response, and the disease control rate (DCR) across all dose levels was 62%. The ORR at the recommended phase 2 doses (RP2D) of 10.0-12.5 mg/kg was 19% (n=3/16) not including one unconfirmed partial response, and the DCR at the RP2D was 69% (n=11/16).

"This is a significant clinical result because current approved anti-angiogenic drugs have little efficacy as a monotherapy. Furthermore, 94% of the colorectal patients and 58% of the gastric patients in this study were previously treated with Avastin (bevacizumab) or Cyramza (ramucirumab), respectively; the response rate is almost three times that seen for current 3rd and 4th line therapies in patients with colorectal and gastric cancers." said Jeeyun Lee, MD, a Professor at the Samsung Medical Center, Seoul, South Korea and the principal investigator of the study.

"The responses to CTX-009 as a monotherapy in this refractory patient population combined with the excellent tolerability profile suggests that CTX-009 can become an important drug for a broad range of solid tumors" said Thomas Schuetz, MD, PhD, CEO and scientific Founder of Compass Therapeutics. "We look forward to developing CTX-009 in the United States and other geographies and to unlocking its full potential". Compass Therapeutics of Boston, Massachusetts holds the global rights to CTX-009 with the exception of S. Korea (rights held by Handok) and China (rights were out-licensed to Elpiscience Biopharma).

"We are pleased to present the clinical data of CTX-009 (ABL001) for the first time at a prominent international conference," said Sang Hoon Lee, PhD, CEO of ABL Bio. "CTX-009 has demonstrated its potential to benefit cancer patients, especially those that have been unable to experience improvements with standard treatments. We expect to further validate the therapeutic value of CTX-009 as it progresses through clinical trials in the U.S., China and South Korea."

"We are happy to see the next frontier of anti-angiogenic therapies, CTX-009 (ES104) showing promising anti-tumor activity in a Phase 1 study as monotherapy," said Steve Chin, MD, CMO of Elpiscience Biopharma, "We look forward to initiating the clinical trials in China to explore its therapeutic potential in the heavily pre-treated digestive tract cancer patients."

About CTX-009

CTX-009 (ABL001/ES104) is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization. Pre-clinical and early clinical data of CTX-009 suggests that blockade of both pathways provides robust anti-tumor activity across several solid tumors, including colorectal, gastric, cholangiocarcinoma, pancreatic and non-small cell lung cancer. Partial responses to CTX-009 as a monotherapy have been observed in heavily pre-treated cancer patients, who were resistant to currently approved anti-VEGF therapies. CTX-009 has completed a Phase 1 monotherapy dose escalation and expansion study. Phase 1b and Phase 2 combination studies are ongoing.

On October 8, 2021 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported it will report financial results for the third quarter 2021 after market close on Thursday, November 4, 2021 (Press release, Guardant Health, OCT 8, 2021, View Source [SID1234591024]). Company management will be webcasting a corresponding conference call beginning at 1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time .

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Live audio of the webcast will be available on the "Investors" section of the company website at: www.guardanthealth.com. The webcast will be archived and available for replay after the event.

On October 8, 2021 Tachyon Therapeutics, Inc. ("Tachyon" or "the Company"), a research and development biotechnology company, reported the presentation of data from its TACH101 program in a virtual poster presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference On Molecular Targets and Cancer Therapeutics being held virtually from October 7-10, 2021 (Press release, Tachyon Therapeutics, OCT 8, 2021, View Source [SID1234591023]).

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Data presented in this abstract and poster are from preclinical studies demonstrating TACH101 target engagement and potency screening to identify molecular biomarkers of response and/or an indication associated with high TACH101 sensitivity. The data showed potent inhibition of gene expression by TACH101 and an increased sensitivity of TACH101 in colorectal cancer, especially those harboring microsatellite instability high (MSI-H) signature.

"Patient selection is critical for the successful development of any drug candidate," stated Frank Perabo, MD, PhD, CEO of Tachyon Therapeutics. "One of the key objectives for our program is to prioritize target indications in which TACH101 is likely to exert most therapeutic benefit. Being able to understand target populations early on generates knowledge that guides clinical trial design, thereby increasing the likelihood of successful transition into clinic."

Highlights from the AACR (Free AACR Whitepaper)-NCI-EORTC abstract and poster presentation are summarized below:

Abstract #P086

RNA-seq evaluation in tumor tissue identified several genes that were up- or downregulated by TACH101, including Protein Phosphatase 1 Regulatory subunit 10 (PPP1R10 or PNUTS).
TACH101 treatment caused 86% repression of PNUTS mRNA, as well as a 51% increase in H3K9me3 (a mark of repressed transcription); a 78% decrease in H3K36me3 at the PNUTS gene was also observed.
Bioinformatics analyses conducted across a large panel of cancer cell lines (>300) showed that cell lines with MSI-H status tended to be more sensitive to TACH101 in vitro. This association was found with other markers of MSI-H status such as MMR gene mutations, MLH1 methylation status, and overall mutation frequency.
To further test this association, TACH101 was evaluated in a panel of patient-derived xenograft (PDX) and organoid models. The results showed a strong correlation of TACH101 sensitivity with MSI-H status (IC50 ranges 1~150 nM).
The virtual poster presentation titled, "Identification of pharmacodynamic and sensitivity biomarkers for TACH101, a pan-inhibitor of KDM4 histone lysine demethylase" is available for on-demand viewing by conference attendees on the AACR (Free AACR Whitepaper)-NCI-EORTC conference website at View Source