On April 15, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, presented new data on the integration of the DecisionDx-Melanoma test with clinicopathologic features (i31-GEP) at the 10th World Congress of Melanoma and 17th European Association of Dermato-Oncology (EADO) Congress (Press release, Castle Biosciences, APR 15, 2021, View Source [SID1234578095]). DecisionDx-Melanoma is Castle’s prognostic gene expression profile test for cutaneous melanoma with an Integrated Test Result (ITR) designed to provide a more precise risk prediction in patients with stage I, II or III melanoma.

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The ITR is calculated by the independently validated integrated 31-GEP, or i31-GEP, algorithm, designed to provide a more precise and personalized prediction of sentinel lymph node (SLN) positivity in order to guide discussions and recommendations, within current risk-based guidelines, for the SLN biopsy (SLNB) surgical procedure. i31-GEP is an artificial intelligence-based neural network algorithm that integrates the DecisionDx-Melanoma test result with the patient’s traditional clinicopathologic features. The algorithm has been validated in a cohort of 1,674 prospectively tested patients with T1-T4 cutaneous melanoma.

The poster, titled "Integration of the 31-gene expression profile test with clinicopathologic features (i31-GEP) to assess sentinel lymph node positivity risk in patients with cutaneous melanoma," highlights the i31-GEP validation study data and demonstrates that the algorithm provides a more precise, personalized likelihood of sentinel lymph node positivity. The poster can be accessed here.

Study methods and findings:

DecisionDx-Melanoma, using the categories of Class 1A, 1B, 2A and 2B, age and tumor thickness was previously validated in an independent, prospective, multi-center study of 1,421 patients to predict SLNB positivity rates.
An integrated DecisionDx-Melanoma test result (i31-GEP) was developed to integrate DecisionDx-Melanoma’s output, a risk assignment based on gene expression profile analysis, with clinicopathologic risk factors.
The study reviewed the development and validation of the i31-GEP, which deploys a neural network algorithm to integrate the continuous DecisionDx-Melanoma score as well as other histologic and clinical features on a development cohort of 1,398 patients. The i31-GEP algorithm was locked using these 1,398 patients and was then independently validated on an independent, U.S. based cohort of 1,674 patients.
The development phase identified that the DecisionDx-Melanoma score was the most important variable in predicting SLN positivity under both the variable importance assessment function (DecisionDx-Melanoma score = 100, Breslow thickness = 56, Mitotic rate = 25, ulceration = 83 and Age = 0; with 100 being the highest possible value) and log-likelihood value (DecisionDx-Melanoma score = 91.3, Breslow thickness = 53.5, Mitotic rate = 20.7, ulceration = 19.1 and Age = 10.5; with 100 being the highest possible value).
The independent validation phase showed that the i31-GEP provides a highly concordant prediction of SLN positivity rate compared to observed rates(linear regression slope of 0.999, with 1.0 representing complete concordance).
Of patients originally classified with 5-10% SLN positivity risk, i31-GEP reclassified 63% of those patients, whose actual risk of SLN positivity was outside that range in either direction (less than 5% or greater than 10%).
i31-GEP had a high negative predictive value of 98% in patients with T1-T4 tumors.
"Most patients who undergo a sentinel lymph node biopsy procedure receive negative results, indicating that other tools may be needed to better understand and stratify risk for patients with melanoma and define groups who may be able to avoid SLNB entirely," said study author Eric Whitman, M.D., surgical oncologist and medical director at Atlantic Health System Cancer Care in New Jersey. "DecisionDx-Melanoma and i31-GEP can help refine patient classification with respect to the likelihood of sentinel node positivity. These clinical validation data show that the ITR result, which reflects a combination of gene expression analysis and standard clinicopathologic features, can be used to provide a more precise risk prediction and potentially help improve patient selection for SLNB."

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. To predict likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithm, i31-GEP, to produce an integrated test result. i31-GEP is an artificial intelligence-based neural network algorithm (independently validated in a cohort of 1,674 prospective, consecutively tested patients with T1-T4 cutaneous melanoma) that integrates the DecisionDx-Melanoma test result with the patient’s traditional clinicopathologic features. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Through December 31, 2020, DecisionDx-Melanoma has been ordered more than 68,920 times for use in patients with cutaneous melanoma.

On April 15, 2021 Alchemab Therapeutics, a biotech company developing novel products for patients with hard-to-treat diseases by harnessing the power of naturally protective antibodies, reported the completion of a £60 million ($82 million) Series A financing round (Press release, Alchemab Therapeutics, APR 15, 2021, View Source [SID1234578119]).

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The international investment syndicate is led by RA Capital Management, with participation from Lightstone Ventures, Data Collective VC (DCVC), DHVC, SV Health Investors and the Dementia Discovery Fund. The company was created by SV Health Investors who led the Seed round in 2019.

The proceeds will be used to advance Alchemab’s unique target-agnostic drug discovery platform. The approach interrogates the entire antibody repertoires of individuals from well-defined groups who show unexpected resistance to disease despite genetic disposition or other risk factors predicative of a poor prognosis. Using insights gained, Alchemab can identify naturally protective antibodies with therapeutic potential. Alchemab’s primary focus is the development of novel therapeutics for hard-to-treat neurodegenerative diseases and cancers, and the Company currently has several programs at the preclinical stage.

Alchemab’s approach was developed with support from scientific founders at Oxford University, Johns Hopkins University and Mount Sinai Hospital. Alchemab is amongst the first commercial group to access Illumina’s Cambridge, UK Accelerator.

"Our aim is to become a major player in the identification of novel targets and antibodies in the areas of neurodegeneration and cancer," noted Alex Leech, CEO at Alchemab. "The substantial financial commitment by this high-caliber group of US and European investors is a strong endorsement of our science and team."

His colleague and co-founder, Dr Jane Osbourn OBE, CSO at Alchemab, added: "Our approach to understanding the natural immunological response to disease and why some people are able to stay well has huge potential to identify antibody therapies across a range of indications. The Series A financing offers a great opportunity to accelerate our efforts to positively impact the lives of patients.

Dr Houman Ashrafian, Managing Partner at SV Health Investors, commented: "Alchemab is a brilliant company driven by science. The Company combines elements of traditional drug discovery techniques with advanced analytics, and in doing so turns the conventional biotech model upside down."

Dr Andrew Levin, Managing Director at RA Capital, added: "It is a privilege to work with this exceptional team. Alex, Jane and the scientists at Alchemab are offering a truly innovative, disease-agnostic approach that we believe has great potential for the development of novel therapeutics."

Last month, Alchemab announced the award of an Innovate UK grant to support the development of a novel disease-modifying antibody therapy for Huntington’s disease, in collaboration with the Medicines Discovery Catapult.

On April 15, 2021 Iktos’s AI technology, reported that based on deep generative models, helps bring speed and efficiency to the drug discovery process (Press release, Iktos, APR 15, 2021, View Source [SID1234580475]). Iktos’ technology automatically designs virtual novel molecules that have all of the characteristics of a successful drug molecule.

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Iktos AI is the first company to release user-friendly and high-performance de novo design software for multi-parameter optimization that can be used by any medicinal or computational chemist, whatever their level of expertise, in deep learning and computer programming.

BioExcel is partnering with Iktos on the application of advanced molecular modelling and simulation techniques to expedite drug design.

On April 15, 2021 Precision BioSciences Inc. (Nasdaq: DTIL), a clinical stage biotechnology company developing allogeneic CAR T and in vivo gene correction therapies with its ARCUS genome editing platform, reported it has entered into a Program Purchase Agreement to reacquire all global development and commercialization rights for all CAR T partnered programs covered under its Development and Commercial License Agreement with Servier (Press release, Precision Biosciences, APR 15, 2021, View Source [SID1234578079]). This includes its two clinical stage CD19-targeting allogeneic CAR T candidates, PBCAR0191 and PBCAR19B stealth cell, as well as four additional product targets.

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"We are excited about the potential of our allogeneic CAR T pipeline to deliver off-the-shelf treatments for patients with cancer," said Matt Kane, CEO and Co-Founder of Precision BioSciences. "We believe we are in a unique position with multiple near-term opportunities to achieve success with allogeneic CAR T cells targeting CD19. Our lead candidate, PBCAR0191, continues to look promising when paired with our enhanced lymphodepletion regimen, and our immune-evading PBCAR19B stealth cell candidate is poised to enter the clinic soon. We seized the opportunity to reacquire these two CD19 programs, as well as four additional targets that were selected by Servier in 2020 to regain global commercial rights and full control of our clinical programs, allowing us to focus our resources and enable rapid decision making."

Under the terms of the Program Purchase Agreement, Servier will receive $1.25 million in cash and Precision has agreed to waive earned, but as-yet unpaid, milestones totaling $18.75 million that would have otherwise been payable to Precision. Servier is also eligible to receive milestones and low- to mid-single-digit royalties subject to product development achievement. With respect to products directed to CD19, Servier has certain rights of negotiation if Precision elects to re-partner the programs.

"Precision was a very good partner for us, and we continue to believe their proprietary, single-step cell engineering technology has the potential to open the door to an off-the-shelf approach for addressing cancer," said Patrick Therasse, Deputy Head of R&D Oncology at Servier. "While we have made the strategic decision to refocus our R&D activities and we will no longer be taking an active role in the Precision programs, we continue to believe they have multiple opportunities, including the stealth cell approach, to benefit patients with hematologic malignancies and solid tumors, so we are pleased to be able to participate in the potential future success of these programs."

Subsequent to Precision’s December 2020 interim Phase 1/2a study data update for PBCAR0191, enrollment in the study has continued, with a focus on dose level 3 (3 x 106 cells/kg) following enhanced lymphodepletion (eLD)1. Initial response rates are consistent with the high response rates reported by Precision in December 2020, and the safety profile continues to be acceptable. Precision intends to monitor the results for durability from this eLD regimen and report updated interim results by mid-2021.

By the end of May 2021, Precision expects to dose the first patient with PBCAR19B, its second CD19 allogeneic CAR T candidate that is engineered with Precision’s proprietary stealth cell technology. Although it has not finalized its full financial results for the first quarter ended March 31, 2021, Precision BioSciences had cash and cash equivalents of approximately $193 million as of March 31, 2021 and continues to expect that cash and cash equivalents, expected operational receipts, and available credit will allow the Company to continue its operations into 2023.

Company-Hosted Conference Call and Webcast Information

Precision’s management team will host a conference call and webcast at 5:00 p.m. ET, Thursday, April 15, 2021 to discuss today’s announcement. The dial-in conference call numbers for domestic and international callers are (866) 996-7202 and (270) 215-9609, respectively. The conference ID number for the call is 8170529. Participants may access the live webcast and the accompanying presentation materials on Precision’s website View Source in the Investors and Media section under Events and Presentations. An archived replay of the webcast will be available on Precision’s website for approximately 30 days.

About PBCAR0191 (Clinical Trials Study Identifier: NCT03666000)

PBCAR0191 is an investigational allogeneic CAR T in a Phase 1/2a clinical trial for the treatment of patients with R/R NHL and R/R B-ALL. PBCAR0191 was designed using Precision BioSciences’ novel and proprietary ARCUS genome editing platform. It has been granted Fast Track Designation by the FDA for the treatment of R/R B-ALL. Precision also holds Orphan Drug Designation from the FDA for this program in mantle cell lymphoma, an aggressive subtype of NHL.

In December 2020, Precision BioSciences reported positive interim results from this study, in which 27 patients with R/R NHL or R/R B-ALL were dosed with PBCAR0191 CAR T therapy and showed no graft versus host disease, no grade ≥ 3 cytokine release syndrome, and no grade ≥ 3 neurotoxicity. For those NHL and B-ALL patients dosed with PBCAR0191, when combined with eLD, objective response rates reached 83% (5/6).

About PBCAR19B (Clinical Trials Study Identifier: NCT04649112)

PBCAR19B is a next-generation, stealth cell candidate for patients with CD19-positive malignancies such as R/R NHL. PBCAR19B is designed to improve the persistence of allogeneic CAR T cells following infusion by reducing rejection by T cells and NK cells. In addition to the CAR gene, the PBCAR19B stealth cell vector carries a short hairpin RNA that suppresses expression of beta-2 microglobulin, a component of Class I Major Histocompatibility Complex (MHC) molecules found on the cell surface. Reducing or knocking-down Class I MHC expression on allogeneic CAR T cells has been shown to reduce CAR T cell killing by cytotoxic T cells. The PBCAR19B vector also carries an HLA-E gene intended to reduce rejection of CAR T cells by NK cells that can be stimulated as a result of reduced MHC molecule expression on the cell surface.

On April 15, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) reported that its first quarter 2021 financial results will be released on Thursday, April 29, after the market closes (Press release, Gilead Sciences, APR 15, 2021, View Source [SID1234578096]). At 4:30 p.m. Eastern Time, Gilead’s management will host a conference call to discuss the company’s first quarter 2021 financial results and will provide a business update.

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A live webcast of the call can be accessed at Gilead’s Investors page at View Source, or by dialing 1-877-359-9508 (U.S.) or 1-224-357-2393 (international) with conference ID 5069935. The webcast will be archived on www.gilead.com for one year.