On May 15, 2020 NuCana plc (NASDAQ:NCNA) reported that two abstracts describing non-clinical studies related to the mechanisms of action of its proprietary ProTides, Acelarin (NUC-1031) and NUC-3373, were selected for poster presentations at the AACR (Free AACR Whitepaper) Annual Meeting 2020 on June 22-24, 2020 (Press release, Nucana BioPharmaceuticals, MAY 15, 2020, View Source [SID1234558115]).

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In prior non-clinical studies, Acelarin has shown an ability to cause cancer-cell death via DNA damage. These new in vitro data presented at AACR (Free AACR Whitepaper) suggest that Acelarin may also have a potential immunomodulatory role. Acelarin was found to cause the release of Damage Associated Molecular Patterns, or DAMPs, and increase the expression of PD-L1 on cancer cells. The findings indicate that Acelarin produces changes in the cancer cells and the tumor microenvironment that could alter the recognition by the immune system, thus potentially making Acelarin an attractive combination partner for immune checkpoint inhibitors.

In the second AACR (Free AACR Whitepaper) abstract, an additional novel mode of action was identified for NUC-3373, NuCana’s ProTide transformation of the active anti-cancer metabolite of 5-fluorouracil (5-FU), a very widely used anti-cancer drug. NUC-3373 was found to be a potent inhibitor of thymidylate synthase, which results in DNA damage of cancer cells. The recent in vitro studies have shown NUC-3373 is able to not only damage DNA, but also induce endoplasmic reticulum stress, and the subsequent release of DAMPs. Thus, in addition to being effective DNA damaging agents in cancer cells, these data suggest that both NUC-3373 and Acelarin may have the potential to alter tumor biology and enhance the activity of immune checkpoint inhibitors.

Hugh S. Griffith, NuCana’s Chief Executive Officer, said: "These findings reveal new and exciting modes of action of our ProTides and help to explain why they appear to be such potent anti-cancer agents."

Acelarin is currently being evaluated in a global Phase III study in combination with cisplatin as a first-line treatment for patients with advanced biliary tract cancer. NUC-3373 is in a Phase Ib clinical study in patients with advanced colorectal cancer in combination with other agents with which 5-FU is typically combined and a Phase I clinical study in patients with advanced solid tumors. NuCana’s third ProTide, NUC-7738, a transformation of a novel nucleoside analog, 3’-deoxyadenosine, is in a Phase I study in patients with advanced solid tumors.

Details of NuCana’s e-poster presentations on June 22-24, 2020: AACR (Free AACR Whitepaper) Virtual Annual Meeting II are as follows:

Abstract Title: NUC-1031 causes release of DAMPs and upregulates PD-L1 expression in lung cancer cells

Poster Number: 1840

Poster Session Title: Mechanisms of Drug Action 2

Abstract Title: NUC-3373 induces ER stress and the release of damage-associated molecular patterns in colorectal cancer cells

Poster Number: 1848

Poster Session Title: Mechanisms of Drug Action 2

Abstracts and full session details can be found at www.aacr.org

On May 15, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that preclinical data for TG-1701, the Company’s highly selective, BTK inhibitor, has been selected for presentation at the upcoming 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, to be held virtually (Press release, TG Therapeutics, MAY 15, 2020, View Source [SID1234558114])

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The presentation details are as follows:

Title: TG-1701, a novel irreversible Bruton’s kinase (BTK) inhibitor, does not inhibit anti-CD20-driven ADCC and ADCP in vitro, and cooperates with the glycoengineered anti-CD20 mAb, ublituximab, in in vivo mantle cell lymphoma models

Abstract Number: 2939
Available on Demand: Monday, June 22, 2020 at 9:00 AM ET
Session Title: Combination Immunotherapies 2
Presenting Author: Gaël Roué, PhD, Lymphoma Translational Group leader, Josep Carreras Leukaemia Research Institute (IJC)
A copy of the above referenced abstract can be viewed online through the AACR (Free AACR Whitepaper) meeting website at www.aacr.org. Following the presentation, the data presented will be available on the Publications page of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On May 15, 2020 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that new translational research for second-generation Bicycle Toxin Conjugate (BTC) BT5528 and preclinical data for novel, fully synthetic tumor-targeted immune cell agonists (TICAs) BT7480 and BT7455 will be presented during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II on June 22-24, 2020 (Press release, Bicycle Therapeutics, MAY 15, 2020, View Source [SID1234558113]). All e-posters will be made available for browsing on AACR (Free AACR Whitepaper)’s e-poster website starting June 22.

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BT5528 is a second-generation BTC, which uses a valine-citrulline cleavable linker and a cytotoxin MMAE payload, that targets EphA2, a tumor antigen that is overexpressed in a wide range of solid tumor types and is associated with poor outcomes. BT7480 is a TICA targeting tumor antigen Nectin-4 and agonizing CD137 (4-1BB). BT7455 is a TICA targeting EphA2 and agonizing CD137.

Details on Bicycle’s poster presentations at AACR (Free AACR Whitepaper) are as follows:

Session Title: Molecular Classification of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes 2
Session Category: Experimental and Molecular Therapeutics
Poster Title: A survey of EphA2 expression by immunohistochemistry (IHC) in tumor tissue microarrays (TMAs) to support BT5528 indication selection
Abstract #: 3302

Session Title: Immunomodulatory Agents and Interventions 2
Session Category: Immunology
Poster Title: BT7480, a novel fully synthetic tumor-targeted immune cell agonist (TICA) induces tumor localized 4-1BB agonism
Abstract #: 5241

Session Title: Immunomodulatory Agents and Interventions 3
Session Category: Immunology
Poster Title: A fully synthetic EphA2/4-1BB tumor-targeted immune cell agonist (TICA) induces tumor localized 4-1BB agonism
Abstract #: 4613

The posters will be available on the Publications section of bicycletherapeutics.com following presentation.

On May 15, 2020 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported that new pre-clinical data evaluating the potential of the lead candidate melflufen (melphalan flufenamide) have been selected for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Oncopeptides, MAY 15, 2020, View Source [SID1234558112]). The poster presentations are now available online.

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Melflufen is a first-in-class anticancer peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Melflufen is in late stage clinical development as a potential treatment of patients with relapsed refractory multiple myeloma (RRMM).

"The annual AACR (Free AACR Whitepaper) meeting is an important forum to present and discuss early-stage data, and we are very pleased that three posters highlighting new data and important insights from our pre-clinical program have been accepted," said Fredrik Lehmann, EVP and CMC at Oncopeptides. "As we continue to evaluate melflufen as a potential treatment for multiple myeloma, and broaden our research to evaluate its potential, we are pleased to highlight data that further evaluate the therapeutic peptide-drug conjugate platform."

Below is a brief description of the three abstracts accepted for poster presentations at this year’s AACR (Free AACR Whitepaper) Annual Meeting including highlights from the presentations. The full AACR (Free AACR Whitepaper) Annual Meeting 2020 abstracts can be found here. View Source!/9045

Title: Prognostic significance of esterase gene expression in multiple myeloma
Presenter: Romika Kumari, MD, Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland

Esterases may play a role in multiple myeloma biology. Their expression levels are dysregulated during disease progression from NDMM to RRMM and several esterases are identified as prognostic markers in myeloma patients.

Title: Melflufen efficacy in multiple myeloma cell lines with TP53 aberrations
Presenter: Ana Slipicevic, Oncopeptides AB, Stockholm, Sweden

Melflufen can trigger myeloma cell death regardless of cells TP53 status and overcome the p53-deficiency-mediated melphalan resistance. Melflufen response rate in the del 17p patient subpopulation from the phase 2-study HORIZON is comparable to the general RRMM population suggesting that melflufen might be a therapeutic option for these difficult-to-treat patients.

Title: Melflufen, a peptide-conjugated alkylator, shows efficacy in breast cancer cell lines
Presenter: Alexander Schepsky, MD, University of Iceland

Melflufen shows high efficacy and selectivity in breast cancer cells compared to their normal derived isogenic counterparts. Efficacy is facilitated by multiple aminopeptidases including CD13, LAP3 and DPP7. This model indicates that melflufen, a peptide drug-conjugate, has an impact on malignantly transformed cells, which cannot be seen in their non-malignant, physiological normal counterpart.

For more information, please contact:
Fredrik Lehmann, EVP Research and CMC at Oncopeptides
E-mail: [email protected]
Phone: +46 8 615 20 40

Rein Piir, Head of Investor Relations at Oncopeptides
E-mail: [email protected]
Cell phone: +46 70 853 72 92

This information was submitted for publication at 12.00 CET May 15, 2020.

About melflufen
Melflufen (melphalan flufenamide) is a first-in-class anti-cancer peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the increased intracellular alkylator concentration. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.

On May 15, 2020 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, and NEC Corporation (NEC; TSE: 6701), a leader in IT and network technologies, reported that they will present data demonstrating that the prediction algorithm used to customize TG4050 for each patient is accurate at identifying immunogenic cancer mutations even among a large set of candidate mutations (Press release, NEC, MAY 15, 2020, View Source [SID1234558111]). These data were jointly generated by the Transgene, NEC and NEC Laboratories Europe GmbH teams and will be presented at the upcoming meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2020 (AACR Virtual Annual Meeting II).

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TG4050 is an individualized therapeutic vaccine based on Transgene’s myvac technology. It is powered by NEC’s cutting-edge AI capabilities. Two Phase 1 trials with TG4050 are ongoing in Europe and in the USA.
TG4050 has been designed to target up to 30 patient-specific neoantigens (cancer cell mutations) which are selected using NEC’s Neoantigen Prediction System, an advanced AI technology that has already been applied in the field of oncology. The prediction system is based on more than two decades of expertise in AI and has been trained on proprietary immune data, allowing it to accurately prioritize and select the most immunogenic sequences.

To evaluate the accuracy of the prediction, samples from cancer patients were collected. Healthy and tumor tissue were sequenced, and mutations were identified and ranked using the algorithm. These were then evaluated by measuring the frequency of T cells against the predicted antigens. Although preliminary, the results generated to-date suggest that the system can identify rare immunogenic mutation among a large list of candidates identified in the patients.

Transgene uses its expertise in viral vectorization to incorporate the selected neoantigen sequences in the genome of the Modified Vaccinia virus Ankara (MVA) viral vector. The Company has set up a unique in-house good manufacturing practice (GMP) unit dedicated to manufacturing the individualized batches of TG4050 needed for the clinical development of this novel individualized therapeutic vaccine.

Title of the poster: « Performance of neoantigen prediction for the design of TG4050, a patient specific neoantigen cancer vaccine »
Authors: Brandon Malone, Caroline Tosch, Benoit Grellier, Kousuke Onoue, Timo Sztyler, Karola Rittner, Yoshiko Yamashita, Eric Quéméneur, Kaïdre Bendjama
Session Date and Time: June 22-24, 2020
Abstract/Poster Number: 4566
The abstract can be downloaded on the AACR (Free AACR Whitepaper) website.

About TG4050
TG4050 is an individualized immunotherapy being developed for solid tumors that is based on Transgene’s myvac technology and powered by NEC’s longstanding artificial intelligence (AI) expertise. This virus-based therapeutic vaccine encodes neoantigens (patient-specific mutations) identified and selected by NEC’s Neoantigen Prediction System. The prediction system is based on more than two decades of expertise in AI and has been trained on proprietary data allowing it to accurately prioritize and select the most immunogenic sequences.
TG4050 is designed to stimulate the immune system of patients in order to induce a T-cell response that is able to recognize and destroy tumor cells based on their own neoantigens. This individualized immunotherapy is developed for each patient and can be produced in a very short time frame.
This best-in-class candidate is being evaluated in two Phase 1 clinical trials for patients with ovarian cancers (new windowNCT03839524) and HPV-negative head and neck cancers (new windowNCT04183166).

About myvac
myvac is a viral vector (MVA) based, individualized immunotherapy platform that has been developed by Transgene to target solid tumors. myvac-derived products are designed to stimulate the patient’s immune system to recognize and destroy tumors using the patient’s own cancer specific genetic mutations. Transgene has set up an innovative network to support the development of myvac individualized immunotherapies that combines bioengineering, digital transformation, established vectorization know-how and unique manufacturing capabilities. Transgene has been awarded an "Investment for the Future" funding from Bpifrance for the development of its platform myvac. TG4050, the first myvac-derived product, is currently being evaluated in two solid tumor clinical trials.

About NEC’s Neoantigen Prediction System
NEC’s neoantigen prediction utilizes its proprietary artificial intelligence (AI), such as graph-based relational learning, which is combined with other sources of data to discover candidate neoantigen targets. NEC comprehensively evaluates the candidate neoantigens, with a primary focus placed on its in-house major histocompatibility complex (MHC) binding affinity prediction trained on public and proprietary datasets. These allow NEC to effectively prioritize the numerous candidate neoantigens identified in a single patient.