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 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported the presentation of preliminary Phase 1 monotherapy clinical data from its Phase 1/2 TRESR (Treatment Enabled by SNIPRx) clinical trial of RP-3500, a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase) for the treatment of solid tumors with specific synthetic-lethal genomic alterations including those in the ATM gene (ataxia teleangectasia mutated kinase), 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, Repare Therapeutics, OCT 8, 2021, View Source [SID1234591015]).

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The data are featured today at the AACR (Free AACR Whitepaper)-NCI-EORTC conference in an oral presentation titled, "First-in-Human biomarker-driven Phase I TRESR trial of ATR inhibitor RP-3500 in patients with advanced solid tumors harboring synthetic lethal genomic alterations" (Abstract number 4950). Preliminary data show that monotherapy RP-3500 is safe and well tolerated, with compelling early efficacy signals across multiple genotypes and tumor types in heavily pretreated patients.

The Company will subsequently host a virtual webcast event today, October 8th at 5:00 p.m. Eastern Time to discuss the latest results from the TRESR trial.

"Our initial data for 101 patients treated with RP-3500 in the ongoing TRESR study resulted in a firm recommendation for Phase 2 dose and schedule, suggest a favorable and differentiated safety profile and provide compelling early evidence of broad clinical efficacy across genotypes predicted by our SNIPRX platform," said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. "The evolving nature of the data from this ongoing study and specifically the stable tolerability profile and maturing efficacy data offer a clear direction for further development of RP-3500. Additionally, we are excited to see that even at this early point in our clinical program, the pharmacokinetic and pharmacodynamic biomarker data already confirm proof-of-mechanism for RP-3500 in tumors with diverse molecular backgrounds."

"The TRESR study is the largest ever biomarker-selected trial testing single agent ATR inhibitor. We are very pleased that these data suggest RP-3500 may have a best-in-class profile as a potent and highly selective ATR inhibitor and represent compelling validation for the ability of our SNIPRx platform and our STEP2 process to improve efficacy through molecular selection of tumors," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "We look forward to the imminent expansion of the TRESR study in a range of genotypes and, continuing and broadening our combination therapy studies, including with a range of PARP inhibitors and gemcitabine."

Key Initial Findings from the TRESR Phase 1/2 Study:

TRESR is a first-in-human, multi-center, open-label Phase 1/2 dose-escalation and expansion study, designed to establish the recommended Phase 2 dose and schedule, evaluate safety and pharmacokinetics and identify preliminary anti-tumor activity associated with RP-3500, given alone and in combination with talazoparib. The study also examined biomarker responses and their relationship with response to RP-3500 treatment.

Data presented in the abstract reflect the monotherapy cohort at data cutoff of June 4, 2021 and include 62 patients, while data presented at the conference reflect a data cutoff of August 15, 2021 and include 101 patients. Highlights from the data presented at the AACR (Free AACR Whitepaper)-NCI-EORTC conference include:

RP-3500 appears safe and well tolerated. The most common treatment emergent adverse events (TEAE) in any of the 101 patients treated, expectedly, was grade 1-2 anemia, with only 21.8% of all patients experiencing Grade 3 anemia (no Grade 4), and only 14.5% of those patients treated on the recommended weekly schedule of 3 days on/4 days off.
There were no discontinuations related to RP-3500 emergent adverse events and dose interruptions, reductions or red blood cell transfusions were infrequent on the recommended 3 days on/4 days off regimen.
Recommended Phase 2 dose (RP2D) and schedule for further monotherapy RP-3500 evaluation is 160mg, taken weekly for 3 days on and 4 days off. This schedule assures repeated weekly exposure to RP-3500 at an efficacious dose.
Antitumor activity was observed in patients with tumors harboring SNIPRX predicted genomic alternations at doses >100mg (ATM, CDK12, BRCA1, BRCA2, RAD51B, RAD51C, FZR1), across multiple tumor types and included patients after PARP inhibitor failure.
Meaningful clinical benefit was observed in 49% of 69 patients with available scans. Those include 12 patients with tumor responses per established international efficacy criteria, 14 patients with ongoing stable disease for at least 16 weeks and 8 patients with stable disease who only had two radiological evaluations, but had demonstrated significant decreases in tumor markers and tumor shrinkage of less than 30%.
Promising deep molecular responses in circulating tumor DNA (ctDNA) for tumors with STEP2 genomic alterations were observed in the initial set of patients available for serial ctDNA analysis
Company Virtual Webcast Event:

The Company will host a virtual investor webcast with accompanying slides for analysts and investors today at 5:00 p.m. Eastern Time to further discuss the RP-3500 data presented 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). Repare’s executive management team will be joined by Timothy Yap, MBBS, PhD, FRCP, Principal Investigator and Medical Director, Institute for Applied Cancer Science, Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, Texas. At this event, the Company will provide an update on the status of the unconfirmed partial responses presented at the AACR (Free AACR Whitepaper)-NCI-EORTC conference since the August 15, 2021 data cutoff.

A live video webcast will be available in the Investor section of the Company’s website at View Source A webcast replay will also be archived for at least 30 days.

About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.

On October 8, 2021 Edouard LEROY Chief Business Officer of Mablink, reported that participates (digitally) in the next edition of the event BIO-Europe, held as a digital event from October 25 to 28, 2021 (Press release, Mablink Bioscience, OCT 8, 2021, View Source;utm_medium=rss&utm_campaign=mablink-is-present-at-bio-europe-2021 [SID1234591016]).

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BIO-Europe is one of the key events dedicated to partnering where global dealmakers meet to build partnerships and discuss investments opportunities.

Edouard will be available for bio-pharma companies, which would be interested in Mablink’s hydrophilic PSARlink ADC platforms or its assets that are available for partnering.

On October 8, 2021 Exact Sciences Corp. (Nasdaq: EXAS) reported that the company plans to release its third quarter 2021 financial results after the close of the U.S. financial markets on November 2, 2021 (Press release, Exact Sciences, OCT 8, 2021, View Source [SID1234591017]). Following the release, company management will host a webcast and conference call at 5 p.m. ET to discuss financial results and business progress.

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An archive of the webcast will be available at www.exactsciences.com. A replay of the conference call will be available by calling 800-585-8367 domestically or 416-621-4642 internationally. The access code for the replay of the call is 2782364. The webcast, conference call and replay are open to all interested parties.

On October 8, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company using its ARCUS genome editing platform to develop allogeneic CAR T and in vivo gene editing therapies, reported that issued the following statement about the safety of its allogeneic CAR T cell therapies (Press release, Precision Biosciences, OCT 8, 2021, View Source [SID1234591036]).

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1) Precision BioSciences’ allogeneic CAR T cells are made using its proprietary ARCUS genome editing platform designed for precision, specificity, and safety.

2) Precision BioSciences’ CAR T cells are the only allogeneic CAR T cells in human clinical trials made with a single gene editing step to specifically avoid the potentially deleterious effects of making multiple edits to T cells.

It is known in the field that making multiple edits in T cells can result in chromosomal abnormalities. Specifically, it has been shown to be an issue in TCR/CD52 edited cells. As published in Cancer Research[1], "Translocation frequencies ranged from 10-4 to 2×10-2 with translocations resulting in acentromeric or dicentromeric chromosomes occurring the least frequently."
Precision’s lymphodepletion strategy does not include an anti-CD52 monoclonal antibody, and therefore does not require editing CD52 in the CAR T cells.
3) In addition, Precision BioSciences believes the oligo-capture method is the most sensitive method available for off-target detection allowing for superior product characterization with respect to gene editing safety. Importantly, this method is used to engineer out off-target editing of the ARCUS nucleases during the research phase of product development.

4) As part of product release testing, Precision BioSciences evaluates chromosomal abnormalities and confirms that the CAR T cells are not transformed.

5) Across four clinical programs in more than 100 patients treated with PBCAR T cells, Precision BioSciences has seen no evidence of chromosomal abnormalities.

Precision BioSciences is actively recruiting patients in ongoing clinical studies of PBCAR0191 (NCT03666000) for patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and R/R B-cell acute lymphoblastic leukemia, PBCAR19B (NCT04649112) for patients with R/R NHL, and PBCAR269 (NCT04171843) for patients with R/R multiple myeloma.