On June 22, 2020 Ascentage Pharma (6855.HK), a global, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and senescence diseases, reported a clinical collaboration with Acerta Pharma, the hematology research and development center of excellence of AstraZeneca (LSE/STO/NYSE: AZN) (Press release, Ascentage Pharma, JUN 22, 2020, View Source [SID1234561370]). Under the terms of the collaboration, Ascentage will sponsor a clinical trial to study the combination of Ascentage Pharma’s APG-2575, a selective Bcl-2 inhibitor, and Acerta’s CALQUENCE (acalabrutinib), a Bruton’s Tyrosine Kinase (BTK) inhibitor, evaluating the efficacy and safety of this combination therapy in patients with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

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This global, multicenter, open-label Phase Ib/II dose-escalation and dose-expansion study is designed to evaluate the safety, tolerability, and anticancer activity of APG-2575 as a single agent or in combination with CALQUENCE in patients with r/r CLL/SLL. The study has already initiated in US with the dosing of first patient, and planned to expand in Europe, and Australia.

CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms and constitutes the most common form of adult leukemia in North America and Europe, accounting for about 30% of all new leukemia cases. Despite significant initial responses to current first-line treatments, many patients with CLL need ongoing treatment to maintain these responses, and relapse often portends a poor prognosis. Recent studies in CLL showed that combining a BTK inhibitor with another Bcl-2 inhibitor can deepen responses and even shorten cyclic treatment, enabling patients to achieve complete remission and therefore discontinue treatment.1,2 These findings have provided a compelling rationale for exploring APG-2575 in combination with BTK inhibitors.

"We are delighted to enter this collaboration with Acerta. APG-2575 is a key drug candidate in our development pipeline targeting apoptosis, with great potential in the treatment of hematologic malignancies. Collaborating with Acerta helps to accelerate our global clinical development program for APG-2575," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "Combination therapy is becoming more important in cancer treatment, and the rationale of a Bcl-2 inhibitor combined with a BTK inhibitor is sound. We hope that APG-2575 combined with CALQUENCE will show synergistic effects in the treatment of CLL/SLL, offering additional treatment options for patients with otherwise limited treatment options around the world."

References

1. Jain N, Keating M, Thompson P, et al. Ibrutinib and venetoclax for first-line treatment of CLL. N Engl J Med 2019;380:2095-2103.
2. Wiestner A. Ibrutinib and venetoclax — doubling down on CLL. N Engl J Med 2019;380:2169-2171.

About APG-2575

APG-2575 is a novel, orally administered Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 is designed to treat a variety of hematologic malignancies by selectively blocking Bcl-2 to restore the normal apoptosis process in cancer cells. Since March 2020, the company has received approvals and clearances for several Phase Ib/II studies of APG-2575 in China, Australia, and the US, and is advancing clinical development of APG-2575 for a variety of hematologic malignancy indications.

On June 22, 2020 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported the presentation of new preclinical data for its folate receptor alpha (FolRα) targeting antibody-drug conjugate, STRO-002, at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II from June 22-24, 2020 (Press release, Sutro Biopharma, JUN 22, 2020, View Source;301080795.html [SID1234561369]). The data, being presented by Sutro’s Chief Scientific Officer, Trevor Hallam, Ph.D., demonstrates STRO-002’s immune-modulating properties and potentiation by PD-L1 blockade.

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The results of the study showed that in FolRα positive tumor cells, STRO-002 treatment induced hallmarks of immunogenic cell death, killing tumor cells while activating immune cells, including monocytes. When combined in mouse tumor models with avelumab, an anti-human & mouse PD-L1 monoclonal antibody, the combination treatment enhanced efficacy leading to more complete responses and increased killer T cells, than either agent alone. Importantly, the data suggest that a single dose of STRO-002 when combined with a PD-1/PD-L1 blockade could provide an effective and protective anti-tumor immune response.

"These data suggest that STRO-002 can drive immune-modulatory responses that can cause complete tumor regression, tumor specific T cell activation and adaptive anti-tumor immunity," said Dr. Hallam. "The results here support the clinical evaluation of STRO-002 in combination with anti-PD1 or anti-PD-L1 agents. While we believe STRO-002 as a single agent may demonstrate clinical benefit in certain tumors resistant to checkpoint inhibitor monotherapies, we are excited at the prospect of evaluating potential additional positive impacts on cancer patients that may result from combination treatment regimens involving STRO-002 with other checkpoint inhibitors."

"An important part of our STRO-002 clinical development strategy includes evaluating these data to determine an optimal combination regimen to take into clinical trials," said Sutro Chief Medical Officer, Arturo Molina, M.D. "We anticipate evaluating STRO-002 in combination studies in addition to our single agent studies. We currently expect to initiate a STRO-002 combination clinical trial in 2021."

STRO-002 is an antibody-drug conjugate directed against FolRα, a membrane receptor glycoprotein, which is highly expressed in ovarian cancer and endometrial cancer and is composed of a FolRα antibody conjugated to a tubulin inhibitor hemiasterlin using a cleavable linker.

A Phase 1, open-label, multicenter, dose escalation trial with dose expansion of STRO-002 is ongoing, designed to identify the maximum tolerated dose, the recommended Phase 2 clinical dose, and to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-002 in adults with advanced epithelial ovarian cancer, including fallopian or primary peritoneal cancer, and endometrial cancer. The trial is registered with clinicaltrials.gov identifier NCT03748186. Sutro discovered, developed and manufactures STRO-002 using its proprietary XpressCF+ cell-free protein synthesis technology.

Presentation Details:

Title: STRO-002, an anti-FolRα ADC, demonstrates immune-modulating properties
and potentiates PD-L1 blockade
Abstract Number: 2250
Session Title: Immune Mechanisms Invoked by Therapies 2
Date/Time: June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT
Presenter: Trevor Hallam, Ph.D.

The e-poster presentation can be found on the AACR (Free AACR Whitepaper) website and is also accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of Sutro Biopharma’s website at www.sutrobio.com on the day of the poster presentation.

Additionally, on June 24th Sutro’s partner Merck KGaA, Darmstadt, Germany, will be presenting preclinical data from the collaboration’s pre-Development Candidate, M1231, a first-in-class bispecific antibody-drug conjugate targeting EGFR and MUC1.

Presentation Details:

Title: M1231: A first-in-class bispecific antibody-drug conjugate targeting EGFR
and MUC1
Abstract Number: 5686
Session Title: Emerging Mechanisms of Resistance to Targeted Therapies
Date/Time: June 24, 2020, 10:05 a.m. – 10:15 a.m. EDT
Presenter: Jan Anderl, Ph.D.

On June 22, 2020 Jubilant Therapeutics Inc., a biopharmaceutical company advancing small molecule modulators to address unmet medical needs in oncology and autoimmune diseases, reported that preclinical data of dual LSD1 and HDAC6 inhibitor JBI-802, will be presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting II (Press release, Jubilant Therapeutics, JUN 22, 2020, View Source [SID1234561368]). The preclinical data demonstrated that JBI-802 has strong efficacy in multiple in vivo cancer models mediated by LSD1 and HDAC6 inhibition, while demonstrating excellent selectivity against other HDACs and superior in vivo efficacy compared to single agents targeting LSD1 or HDAC6.

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"We are excited to reveal these new data from our study of JBI-802 whose first-in-class dual mechanism of action targets the overexpression of two proteins, while exhibiting a favorable tolerability profile," said Syed Kazmi, President and Chief Executive Officer of Jubilant Therapeutics Inc. "These data support the additional development of this novel dual epigenetic inhibitor as a potential therapeutic agent for genetically-defined cancers."

A link to the e-poster, listed below, is available through the AACR (Free AACR Whitepaper) website.

Title: Novel Dual Small Molecule Inhibitor Targeting LSD1 and HDAC6
Poster Number: 1756
Date and Time: June 22, 2020 at 8:45 a.m. Eastern Daylight Time (EDT)
Session Title: Epigenetic Targets
Presenter: Dhanalakshmi Sivanandhan, et al.

Key highlights from the study which examined anti-proliferative activity of JBI-802 on select acute myeloid leukemia (AML), chronic lymphocytic leukemia, small cell lung cancer, sarcoma and multiple myeloma cell lines as compared to single agents, include the following:

JBI-802 demonstrated strong tumor growth inhibition in erythroleukemia and multiple other hematological tumors as compared to single agents;
Syngeneic models showed single agent activity with unique mechanism of action and that JBI-802 can be combined with checkpoint inhibitors safely in this mouse model; and
The molecule showed a favorable tolerability profile at efficacious doses.
JBI-802 is currently being evaluated in IND-enabling studies for the treatment of AML and other solid tumors and first-in-human clinical studies are expected in 1H 2021. Jubilant Therapeutics Inc. is developing a pipeline of novel, differentiated therapeutic assets; for partnership opportunity inquiries please contact [email protected].

On June 22, 2020 ESSA Pharma Inc. (Nasdaq: EPIX); (TSXV: EPI), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported new preclinical data on ESSA’s clinical candidate, EPI-7386, at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Virtual Annual Meeting II (Press release, ESSA, JUN 22, 2020, View Source [SID1234561367]).

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In an oral poster presentation titled, "Preclinical development of the second-generation N-terminal domain androgen receptor inhibitor, EPI-7386, for the treatment of prostate cancer", a robust preclinical characterization of EPI-7386 including androgen receptor (AR) binding, gene expression analyses and the toxicologic profile was presented. The studies highlight new information about EPI-7386 including:

Full-length AR target engagement by EPI-7386 was confirmed in a cellular thermal shift assay.
In vitro cellular gene expression analyses demonstrate that EPI-7386:
Inhibits AR transcriptional activity similar to enzalutamide but with a few notable qualitative and quantitative differences in an enzalutamide-sensitive cellular model.
In the same cellular model, combination treatment of EPI-7386 with enzalutamide displays broader and deeper inhibition of AR-associated transcriptional activity than higher doses of each single agent alone.
Shows superior activity to enzalutamide in an AR-V7-driven cellular model by modulating both AR-FL and AR-V7-driven gene expression.
Toxicology studies evaluating the safety profile of EPI-7386 demonstrate that:
Very high plasma exposures of EPI-7386 were achieved across all studies.
Tolerability in 28-days tox studies in rats and dogs at AUC ≤ 2,000,000 ng*hr/mL, with activity seen on androgen-sensitive target organs in dogs.
The highest doses tested were characterized as the HNSTD (highest non-severely toxic dose) and only exhibited body weight loss and reduced food consumption. The drug plasma exposures achieved at this high dose were 7-10 fold higher than the efficacious exposures achieved in mouse xenograft models.
The starting clinical dose of EPI-7386 will be 200 mg given once-daily
"Our latest transcriptomic analyses add to the breadth of preclinical data supporting the development of EPI-7386 broadly in prostate cancer. With the favorable toxicologic profile of EPI-7386 observed in our IND-enabling studies at very high exposures, we will initiate dosing at 200 mg per day, which potentially could allow us to efficiently reach biologically relevant blood levels of EPI-7386 in patients," said Dr. David R. Parkinson, President & Chief Executive Officer. "We will soon begin dosing patients in our Phase 1 monotherapy study of EPI-7386 in castration-resistant prostate cancer patients whose tumors are progressing on current anti-androgens.".

On June 22, 2020 Aethlon Medical, Inc. (Nasdaq: AEMD), a therapeutic medical device and technology company focused on unmet needs in viral diseases, oncology and inflammation, reported positive ex vivo data demonstrating the ability of a laboratory version of the Company’s Hemopurifier to capture tumor-derived exosomes in several forms of cancer (Press release, Aethlon Medical, JUN 22, 2020, View Source [SID1234561366]). The data were presented in e-poster format by Dr. Annette Marleau, the Company’s Senior Director of Research, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, on June 22, 2020.

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Exosomes are subcellular particles that are shed from both normal and malignant cells and have been shown to mediate multiple mechanisms of tumor growth and spread. The e-poster, titled, "Targeting Tumor-Derived Exosomes using a Lectin Affinity Hemofiltration Device", highlights data from ex vivo studies which demonstrate that a laboratory version of the Hemopurifier effectively captures and removes substantial quantities of exosomes from fluid samples that are circulated through the device. The data show that the Hemopurifier can clear exosomes that originate from plasma from patients with diverse cancers, including head and neck cancer, melanoma, ovarian cancer, esophageal cancer and breast cancer. The e-poster is available online at View Source!/9045/presentation/7490.

"Despite abundant research on tumor-derived exosomes and their role in cancer growth and immunosuppression, a clinical strategy for influencing exosomes in oncology has been unavailable," said Timothy C. Rodell, M.D., Chief Executive Officer of Aethlon. "The ability to effectively target and capture exosomes that exhibit signatures of malignancy and immunosuppression offers a potentially powerful therapeutic strategy for cancer. By reducing the presence of tumor-derived exosomes in the circulation of cancer patients, we believe the Hemopurifier may have the potential to improve the benefits of existing cancer treatment regimens and emerging immuno-oncology drugs. Our recently announced Early Feasibility Study in patients with head and neck cancer being treated with pembrolizumab (KeytrudaÒ) may provide human clinical data to complement these in vitro studies."