On June 22, 2020 BERG, a clinical-stage biotech that employs artificial intelligence (AI) to research diseases and develop innovative treatments, reported five presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting, being held from June 22- 24, 2020 (Press release, Berg, JUN 22, 2020, View Source [SID1234561365]).

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Two presentations feature outputs of the BERG Interrogative Biology platform. One focuses on BERG’s Interrogative Biology discovered oncology target BPM 42522, its lead molecule, and mechanism of action leading to its anti-cancer properties. The other highlights validation of the BERG pan-cancer model by an independent study (Behan FM et al., (Nature, 2019 Apr 10). Three other presentations demonstrate the translational impact from current collaborations with institutions including BIDMC/Harvard, Stanford University and Uniformed Services University of the Health Sciences along with Walter Reed National Military Medical Center.

"We are making significant advances with BERG’s Interrogative Biology platform, by partnering with several thought leaders in the field of oncology at the upcoming AACR (Free AACR Whitepaper) meeting," said Dr. Niven R. Narain, BERG Co-founder, President and Chief Executive Officer. "This week, we will present the preliminary results of a lead molecule that modulates BPM 42522, as a direct result from BERG’s platform as well. None of this would be possible without the continued support of our partners around the world."

"BERG’s pioneering work in analyzing large molecular datasets with Bayesian Artificial Intelligence for identification of therapeutic targets with high translational potential, clearly illustrates the impact of our work in improving drug discovery as well as the success rates of our developments," said Professor Vikas P. Sukhatme, M.D., Sc.D., Dean of the Emory School of Medicine, Chief Academic Officer of Emory Healthcare, and a member of BERG’s Scientific Advisory Board.

Presentation Details at the AACR (Free AACR Whitepaper) Virtual Meeting:

Presentation title

Abstract title/number

Presenters

Date/time

Identification of Molecular Targets 2

Interrogative Biology platform identifies a ubiquitin pathway and its utility in cancer is supported by small molecule modulators

Abstract # 2943/17

Stephane Gesta, Shefali Sharma, Pragalath Sundararajan, Mingshu Huang, Kayleigh Gray, Maria Nastke, Arcan Guven, Anne Diers, Shiva Kazerounian, Suwagmani Hazarika, Eric M. Grund, Vivek K. Vishnudas, Niven R. Narain, Rangaprasad Sarangarajan

June 22, 2020

9:00am-6:00pm

Virtual Meeting II: E-Posters

Mechanisms of Drug Action 3

BPM31510, a Coenzyme Q10 (CoQ10) containing lipid nanodispersion, enhances radiation effects to prolong survival in a rodent glioblastoma model

Abstract # 2968/15

Jiaxin Sun, Milton Merchant, Anne R. Diers, Shiva Kazerounian, Stephane Gesta, Niven R. Narain, Rangaprasad Sarangarajan, Seema Nagpal, Lawrence Recht

June 22, 2020

9:00am-6:00pm

Virtual Meeting II: E-Posters

Recent Biomarker Discovery Techniques

Impact of hemolysis on multi-omic pancreatic cancer biomarker discovery: Derisking precision medicine biomarker development

Abstract # 2860/14

Michael A. Kiebish, Punit Shah, Valerie Bussberg, Vladimir Tolstikov, Rick Searfoss, Kennedy Ofori-Mensa, Eric M. Grund, Abena Darkway, Emily Y. Chen, Bennett Greenwood, Ellaine Adu Ntoso, Leonardo Rodrigues, Mia Liu, Elder Granger, Chas Bountra, Rangaprasad Sarangarajan, A J. Moser, Niven R. Narain

June 22, 2020

9:00am-6:00pm

Virtual Meeting II: E-Posters

Molecular Classification of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes 2

Integrated proteomic and informatic assessment of ER+HER2- and ER-/HER2-breast tumors

Abstract # 5311/20

Guisong Wang, Punit Shah, Vladimir Tolstikov, Praveen-Kumar Raj-Kumar, Jiafang Liu, Lori A. Sturtz, J. Leigh Fantacone-Campbell, Rebecca Zingmark, Jeffrey A. Hooke, Mary L. Cutler, Kris Richardson, Leonardo Rodrigues, Valerie Bussberg, Rangaprasad Sarangarajan, Niven R. Narain, Hai Hu, Michael A. Kiebish, Albert J. Kovatich, Craig D. Shriver

June 22, 2020

9:00am-6:00pm

Virtual Meeting II: E-Posters

Identification of Molecular Targets 2

Benchmarking targets from cancer models using causal interference based drug-target and phenotype identification (Interrogative Biology) cross-validates "high-priority" targets identified in CRISPR-CAS9 screen

Abstract #2929/3

Leonardo O. Rodrigues, Lixia Zhang, Poornima Tekumalla, Stephane Gesta, Vivek K. Vishnudos, Michael A. Kiebish, Niven R. Narain, Rangaprasad Sarangarajan

June 22, 2020

9:00am-6:00 pm

Virtual Meeting II: E-Posters

Full abstracts of the posters are available on the AACR (Free AACR Whitepaper) web site at View Source!/9045.

On June 22, 2020 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) ("CBMG" or the "Company"), a biopharmaceutical firm engaged in the drug development of immunotherapies for cancer and stem cell therapies for degenerative diseases, today presented a poster during the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting to be held as a virtual meeting from June 22-24, 2020 (Press release, Cellular Biomedicine Group, JUN 22, 2020, View Source [SID1234561364]).

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Poster Title:

"Selecting Clinical Lead of TCRs Targeting Alpha-Fetoprotein-Positive Liver Cancer on Balance of Risk and Benefit"

Session:

Session PO.IM02.04 – Adoptive Cell Therapy 5

Poster No:

6589 (Board 1)

Authors:

Cellular Biomedicine Group, Inc, Gaithersburg, MD;

Georgia Cancer Center, Augusta University, Augusta, GA

Date:

Monday, June 22, 2020

Time:

9:00 a.m.to 6:00 p.m. EDT

Location:

San Diego Convention Center, Exhibit Halls A-F, Poster Virtual Meeting II:

E-Posters

Website:

View Source!/9045/presentation/7124

C-TCR055 is CBMG’s proprietary clinical lead of TCR-T which specifically recognizes the HLA-A*02:01 restricted AFP158-166 peptide that is highly expressed in hepatocellular carcinoma (HCC) and other solid tumors. Preclinical studies suggested that C-TCR055 has optimal anti-tumor activities and a good safety profile. CBMG is currently conducting a Phase I clinical study in unresectable HCC in Fudan University Affiliated ZhongShang Hospital in Shanghai, China (NCT03971747).

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with a poor prognosis and limited therapeutic options. Alpha-fetoprotein (AFP), an established clinical biomarker of HCC, has been employed as an attractive target for T cell-based immunotherapy against this disease given its high expression in the tumor and restricted expression in normal tissues. We have identified a number of T cell receptors (TCRs) recognizing the HLA-A*02:01 restricted AFP158-166 peptide FMNKFIYEI, providing a TCR candidate pool for identifying TCRs with optimal clinical benefit.

Methods: To select the ideal AFP TCR for clinical use, we evaluated the efficacy and safety profile of 7 TCRs on balance of their potency and specificity by testing their reactivity to normal and transformed cells covering a variety of primary cell types and HLA serotypes, and potential protein candidate in human genome by an extensive alanine scan (X-scan).

Results: We first selected three TCR candidates based on the in vitro anti-tumor activity. Next we eliminated two potential cross-reactive TCRs based on their reactivity against normal and transformed cells covering a variety of primary cell types and HLA serotypes, respectively. We then excluded the potential cross-reactivity of the selected TCR with protein candidates in human genome identified by X-scan.

Conclusion: To date we have selected an AFP TCR with the optimal affinity, function, and safety profile, bearing properties that are expected to allow AFP TCR redirected T cells to specifically differentiate between AFP levels on tumor and normal tissues. An early phase clinical trial using T cells transduced with this TCR to treat HCC patients (NCT03971747) has been initiated.

On June 22, 2020 Rakuten Medical, Inc. (Rakuten Medical) reported the results of two preclinical studies presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting II (Press release, Rakuten Medical, JUN 22, 2020, View Source [SID1234561363]). These studies further demonstrate the mechanism of action of Rakuten Medical’s Illuminox technology platform with its antibody-IRDye 700DX conjugate and how this unique technology induces tumor cells and enhances the adaptive immune response.

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"We are excited to present data on the mechanism of action of the Illuminox technology to induce rapid cell membrane disruption of cells targeted with the antibody-IRDye 700DX conjugate and the induction of cell necrosis and immunogenic cell death," said Miguel Garcia-Guzman, Ph.D., Chief Scientific Officer, Rakuten Medical. "Consistent with this mechanism of action, the study also shows that Illuminox treatments induce robust anti-cancer effects in immunocompetent animals by activating tumor specific innate and adaptive anticancer immunity with long term immune memory."

The following preclinical poster presentations were showcased during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting II:

"Molecular mechanism of action of photoimmunotherapy with antibody-IR700 dye conjugates: Role of singlet oxygen in cell membrane disruption and necrotic cell death." (Abstract 480), presented by Roger Heim, Rakuten Medical.

This poster investigates the mechanism of action of Rakuten Medical’s proprietary Illuminox photoimmunotherapy through a series of preclinical experiments. These data describe the unique biophysical processes by which photoimmunotherapy with antibody-IR700 dye damages cell membranes and induces cell death.

"Anticancer activity by photoimmunotherapy is driven by adaptive immune responses and induces vaccinal effects in mice." (Abstract 949), presented by C. Daniel De Magalhaes Filho, Rakuten Medical.

This poster confirms previous data demonstrating that photoimmunotherapy induces cell death in tumor cells and ignites an immune response against the tumor [Hsu M, et al. AACR (Free AACR Whitepaper) 2019].

In this study, mice implanted with photoimmunotherapy-treated tumor cells rejected new tumor challenges, indicating that photoimmunotherapy induces immunogenic cell death and activates immune responses in the host mice protecting against future tumor challenges.

On June 22, 2020 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematologic and oncologic diseases, reported findings on the investigational cyclin-dependent kinase 9 (CDK9) inhibitor alvocidib and TP-1287, an oral prodrug of alvocidib (Press release, Tolero Pharmaceuticals, JUN 22, 2020, View Source [SID1234561362]). These data, highlighting a novel biomarker detection method for CDK9 inhibition and evaluating the anti-tumor activity of alvocidib and TP-1287 in hematologic cancer cells, are being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting II, taking place June 22-24, 2020.

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The virtual poster presents a novel biomarker detection method to assess CDK9 inhibition through reduction of myeloid cell leukemia-1 (MCL-1) expression and of phosphorylation of RNA polymerase II (p-RPB1). Using peripheral blood mononuclear cells (PBMCs) as a surrogate tissue, this method was able to identify CDK9 inhibition in healthy donor PBMCs treated with alvocidib, the active form of TP-1287, ex vivo. This was also identified in a Phase 1 study participant receiving TP-1287 in an ongoing trial in patients with refractory solid tumors. These data may suggest a novel clinical biomarker approach for assessing overall CDK9 inhibition in patients.1

In preclinical studies, TP-1287 and alvocidib also showed potent cell-based activity in vitro and tumor growth inhibition in vivo across multiple hematologic cell lines, including acute myeloid leukemia (AML) and multiple myeloma (MM). Alvocidib was found to suppress p-RPB1 and the transcription of MCL-1, both downstream effectors of CDK9 activation, across cell lines and in normal PBMCs. Separately in a MM xenograft model, TP-1287 was shown to inhibit tumor growth, suppress p-RPB1 and the transcription MCL-1, and induce apoptosis.1

"Together, the results presented at AACR (Free AACR Whitepaper) show the inhibitory downstream effects of TP-1287 and its active form, alvocidib, across multiple AML and MM cell lines and in in vivo mouse models, which can be measured by a novel biomarker detection method," said David J. Bearss, Ph.D., Chief Executive Officer, Tolero Pharmaceuticals, and Chief Scientific Officer and Global Head of Research, Global Oncology. "Given the identification of this novel biomarker detection method to assess CDK9 inhibition, and the ability of TP-1287 to deliver alvocidib in the clinic, these findings support continued evaluation of the potential of CDK9 inhibition and the use of surrogate biomarkers in the ongoing study of TP-1287."

Below are the details for the presentation:

Abstract Title

Details

Author

Pharmacodynamic biomarker strategies
for CDK9 inhibition

Abstract# 5813

June 22, 2020

9 a.m. ET

Poster Presentation

Yuta Matsumura, Tolero
Pharmaceuticals

About TP-1287

TP-1287 is an investigational oral cyclin-dependent kinase 9 (CDK9) inhibitor under evaluation in a Phase 1 study in patients with advanced solid tumors (NCT03604783). TP-1287 has shown favorable oral bioavailability in preclinical models.

About Alvocidib

Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in the ongoing Phase 2 Zella 202 study in patients with acute myeloid leukemia (AML) who have either relapsed on or are refractory to venetoclax in combination with azacitidine or decitabine (NCT03969420). Alvocidib is also being evaluated in Zella 102, a Phase 1b/2 study in patients with myelodysplastic syndromes (MDS) in combination with azacitidine or decitabine (NCT03593915), and in a Phase 1 study in patients with relapsed or refractory AML in combination with venetoclax (NCT03441555).

About CDK9 Inhibition and MCL-1

MCL-1 is a member of the apoptosis-regulating BCL-2 family of proteins.2 In normal function, it is essential for early embryonic development and for the survival of multiple cell lineages, including lymphocytes and hematopoietic stem cells.3 MCL-1 inhibits apoptosis and sustains the survival of leukemic blasts, which may lead to relapse or resistance to treatment.2,4 The expression of MCL-1 in leukemic blasts is regulated by cyclin-dependent kinase 9 (CDK9).5,6 Because of the short half-life of MCL-1 (2-4 hours), the effects of targeting upstream pathways are expected to reduce MCL-1 levels rapidly.5 Inhibition of CDK9 has been shown to block MCL-1 transcription, resulting in the rapid downregulation of MCL-1 protein, thus restoring the normal apoptotic regulation.2

on June 22, 2020 twoXAR Pharmaceuticals, a drug discovery and development company focused on bringing first-in-class small molecules to market, reported that preclinical data for its investigational treatment TXR-311 with a novel MOA demonstrated significant efficacy and good tolerability in in vivo studies for the potential treatment of hepatocellular carcinoma (HCC), with results comparable to sorafenib, today’s standard-of-care (Press release, TwoXAR, JUN 22, 2020, View Source [SID1234561361]). The data was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II. The full poster and accompanying audio of the data is available at www.twoxar.com.

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"We are pleased that our TRX-311 in vivo data was selected for presentation at AACR (Free AACR Whitepaper). This study is another demonstration that our approach to drug discovery is effective in identifying novel molecules that have high likelihood of showing positive safety and efficacy signals in preclinical studies," stated Andrew A. Radin, co-founder and CEO of twoXAR. "We are thrilled with the progress of our HCC clinical program thus far and look forward to advancing additional drug candidates in disease areas with similar unmet needs."

HCC is a complex and heterogenous tumor and the most common type of primary liver cancer. It is difficult to diagnose and treat, with poor survival. It is most commonly associated with underlying chronic liver disease, including hepatitis and alcoholic and non–alcoholic steatohepatitis (NASH).

"While we have some beneficial treatments for hepatocellular carcinoma, this tumor type is a growing problem worldwide and more options are needed," said Dr. Ghassan K. Abou-Alfa, MD, medical oncologist at Memorial Sloan Kettering. "These early results are interesting and exciting because they showed safety and efficacy comparability against sorafenib but with a completely novel mechanism of action."

In validation studies, TRX-311 demonstrated greater activity and selectivity in killing HCC tumor cells than standard of care, sorafenib, and significantly inhibited growth in two HCC patient-derived xenograft (PDX) tumor models. TRX-311 also demonstrated in vivo efficacy comparable to sorafenib with good tolerability.

As part of a larger oncology drug discovery program, twoXAR identified 10 novel MOAs each for HCC and pancreatic ductal adenocarcinoma (PDAC) through its AI-driven drug discovery approach that builds an in-silico disease model using multiple sets of biological, clinical and chemical data. TRX-311 showed the most promising results and was chosen to proceed into lead optimization studies for HCC. TRX-311 also showed in vitro activity at low µm concentrations in PDAC cancer cells.

About Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) occurs most often in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. HCC is a multifactorial disorder and does not cause symptoms in the early stage, which often leads to a delay in diagnosis. The exact cause of HCC is not fully understood.