On December 7, 2020 Menarini Group reported that it will present the results of two different preclinical studies on MEN1611, a potent and selective phosphatidylinositol 3-kinase inhibitor (PI3Ki) currently in clinical development for the treatment of breast cancer, at the upcoming 2020 San Antonio Breast Cancer Symposium, which will be held virtually on December 8-11 (Press release, Menarini, DEC 7, 2020, View Source [SID1234572389]).

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"We are pleased to present at the San Antonio Breast Cancer Symposium and look forward to discussing in more detail the encouraging preliminary results achieved by our preclinical studies on MEN1611," commented Andrea Pellacani, General Manager of Menarini Ricerche, R&D Division of the Menarini Group. "This data contributes to a greater understanding of the mechanism of action of MEN1611 and further support its clinical development for the treatment of breast cancer, reinforcing our strong commitment to advancing precision oncology to the benefit of patients living with difficult-to-treat cancer."

MEN1611 is a potent and selective PI3Ki targeting the p110 α, β and γ isoforms, while sparing the δ subunit. B-PRECISE-01 is a multicenter, Phase Ib, dose escalation and expansion study, investigating MEN1611 in patients with HER2-positive, PIK3CA mutated, advanced or metastatic breast cancer.

The poster entitled "MEN1611 is a PI3K α/β selective and δ sparing inhibitor with long-lasting antitumor activity in different genetic backgrounds of PIK3CA mutant breast cancer models" presents the results of a preclinical study on the antitumor activity of MEN1611 in p110 α- and β-dependent tumors, providing evidence that in these animal models MEN1611 is active against HER2-positive, PIK3CA mutated and PTEN-null breast tumor.

A second poster, entitled "MEN1611 promotes immune activating myeloid cell polarization" presents the results of a study aimed at characterizing the effects of MEN1611 on the PI3Kγ isoform, highly expressed in tumor-associated macrophages, to investigate whether the anti-tumor activity of MEN1611 might also be mediated by MEN1611-mediated modulation of tumor inflammatory microenvironment. The results of this study show that MEN1611 inhibition of the PI3Kγ isoform leads to macrophage reprogramming, from an immune-suppressive to an immune-activating phenotype. Moreover, the tumor regression induced by MEN1611 was associated to changes of the inflammatory microenvironment, characterized by an increased recruitment of T cells, which may contribute to the anti-tumor activity of MEN1611 in this model.

About MEN1611

MEN1611 is a potent and selective PI3K inhibitor targeting the p110 α, β and γ isoforms, while sparing the δ subunit. It is an investigational compound, not approved for use by regulatory authorities, currently being evaluated in the B-PRECISE-01 trial (clinicaltrials.gov identifier: NCT03767335), and in the C-PRECISE-01 trial (clinicaltrials.gov identifier: NCT04495621) for the treatment of breast cancer and colorectal cancer, respectively.

On December 7, 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 cancer and autoimmune therapeutics, reported a poster presentation at the virtual 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting for the ongoing Phase 1 dose-escalation clinical trial for its CD74-targeted antibody drug conjugate (ADC) STRO-001 for patients with late-line Non-Hodgkin Lymphoma (NHL) (Press release, Sutro Biopharma, DEC 7, 2020, View Source [SID1234572388]). Additionally, data were presented from preclinical studies conducted in collaboration with researchers from the Fred Hutchinson Cancer Research Center.

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"With three product candidates in the pipeline actively enrolling patients—STRO-001, STRO-002, our folate receptor alpha- (FolRα) targeting ADC, and CC-99712 in partnership with Bristol Myers Squibb, a BCMA-targeting ADC—Sutro is working on addressing unmet needs via targeted therapies that can tackle cancer evolution," said Bill Newell, Sutro’s Chief Executive Officer. "The encouraging safety and preliminary efficacy clinical data presented at ASH (Free ASH Whitepaper) on STRO-001 for the treatment of late-line NHL further validates our platform and unique approach to ADC design, creating potential first-in-class and/or best-in-class therapeutic candidates."

STRO-001 Phase 1 Dose Escalation Interim Data
STRO-001-BCM1 is an ongoing first-in-human, phase 1 dose-escalation study evaluating the safety, tolerability, and preliminary antitumor activity of STRO-001 in adults with B-cell malignancies. The study is ongoing, and data presented at ASH (Free ASH Whitepaper) included results from the NHL cohort. There were 21 NHL patients treated and 18 evaluable patients for response. Patients had a median of 5 prior therapies. 6/21 patients (29%) had previous stem cell transplant or CAR-T therapy. Data as of October 30, 2020 are as follows:

Most (90%) treatment-emergent adverse events (TEAEs) were grade 1 or 2 and no ocular or neuropathy toxicity signals have been observed
Following a previously announced protocol amendment last year requiring pre-treatment screening imaging for patients at risk for thromboses, no additional thromboembolic events have been observed
In the 7 patients with diffuse large B-cell lymphoma (DLBCL), 1 complete response (CR) and 2 partial responses (PRs) were observed
Out of other NHL types, 2 patients with follicular lymphoma had stable disease (SDs), of which one is still on treatment at 9 weeks. One patient with marginal zone lymphoma had SD and is still on treatment at 39 weeks
"These results continue to demonstrate the potential clinical benefit of STRO-001 treatment in patients with NHL who are heavily pretreated, with a median of five prior lines of treatment," said Dr. Arturo Molina, Sutro’s Chief Medical Officer. "We are especially pleased for the patients who responded to STRO-001 after previously progressing on CAR-T treatments and an additional post- CAR-T regimen to which they had no response, seeing comparable duration of disease control to the duration on a cell therapy. STRO-001 has been well tolerated. We look forward to continuing the dose-escalation study to learn more about the potential for STRO-001 for patients with NHL."

Maximum tolerated dose (MTD) was not reached at 2.5 mg/kg. Active enrollment in the NHL cohort continues at the 3.5 mg/kg dose level and additional higher dose levels may be explored. The trial, registered with clinicaltrials.gov identifier NCT03424603, continues to enroll patients in dose escalation in both multiple myeloma (MM) and NHL cohorts.

The virtual poster titled "Preliminary Results of an Ongoing Phase 1 Dose Escalation Study of the Novel Anti-CD74 Antibody Drug Conjugate (ADC), STRO-001, in Patients with B-cell Non-Hodgkin Lymphoma," presented by Nirav N. Shah, M.D., Associate Professor of Medicine at Medical College of Wisconsin, is accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of the company’s website at www.sutrobio.com.

Preclinical Data from Fred Hutchinson Cancer Research Center in Collaboration with Sutro
Fred Hutchinson Cancer Research Center, in collaboration with Sutro, presented preclinical models showing the potential of CD74-targeted therapies, and in particular STRO-001, for the treatment of acute myelogenous leukemia (AML). The research is out of the lab of Soheil Meshinchi, M.D., Ph.D., Professor, Clinical Research Division at Fred Hutchinson Cancer Center and Professor of Pediatrics at University of Washington School of Medicine.

"My team at Fred Hutchinson Cancer Research Center has built a robust computational platform leveraging our large AML transcriptome dataset to identify highly expressed antigens on leukemic cells that are being targeted by agents in early phase trials or preclinical development with the goal of repurposing these therapeutics for use in AML," said Soheil Meshinchi, M.D., Ph.D. "One of these therapies was the STRO-001 ADC which targets the cell surface protein CD74. We have demonstrated that CD74 is highly expressed in a significant proportion of patients with AML. Our initial studies of STRO-001 ADC in AML cell lines demonstrated robust in vitro cytotoxicity on AML cell lines expressing high- to moderate-levels of CD74, with no cytotoxicity in cells with no CD74 expression. This in vitro data, which identifies CD74 as a viable target in AML, coupled with the 27% incidence of CD74 in nearly 1,000 pediatric AML patients from our clinical trial with bortezomib, strengthens the notion that targeting CD74 with STRO-001 represents a viable targeted therapy in this patient population. In addition to AML, CD74 is highly expressed in high risk acute lymphoblastic leukemia (ALL), including Ph-positive and Ph-like ALL, thus providing rationale for exploring the efficacy of STRO-001 in all leukemias.

A virtual poster titled "Target-Informed Repurposing of Immunotherapies in AML – a Transcriptome Based Approach for Identifying Immediately Available Therapeutics," will be presented Amanda Leonti, MS, Computational Biology, Meshinchi lab, Fred Hutchinson Cancer Research Center, and include in vitro cytotoxicity data for STRO-001 in AML cell lines. See the abstract here.
A virtual oral session titled "Newly Diagnosed Childhood AML Patients Treated with Bortezomib Show Superior Survival If CD74 Is Expressed: A Report of 991 Patients from the Children’s Oncology Group AAML1031 Protocol," will be presented by Lisa Eidenschink Brodersen PhD HCLD, Director, Flow Cytometry, Hematologics, Inc in Seattle Washington, and will highlight the potential of CD74 targeted therapies in pediatric AML. See the abstract here.

On December 7, 2020 Beijing Biocytogen Co., Ltd., Biocytogen Boston Corp (collectively as "Biocytogen") reported that they have reached an agreement with Xencor, Inc., for the licensing of Biocytogen’s fully human antibody RenMab/RenLite Mouse platform to enhance Xencor’s monoclonal antibody drug discovery research (Press release, Biocytogen, DEC 7, 2020, View Source [SID1234572386]).

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The leading platform for fully human antibody generation

The RenMab Mouse was developed using Biocytogen’s unique chromosome engineering technique. In this model, the Ig genes that encode for antibody variable domains of heavy and κ light chains are fully replaced by human corresponding Ig genes . The RenLite Mouse is a genetically engineered model with complete humanization in the variable region of the heavy chains, while maintaining a single human light chain. These models can be used to fast generate and screen fully human antibody hits and thus identify therapeutic candidates with high affinities, specificities, and diversities more efficiently than by using other available technology platforms.

Xencor is a leading clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases. Xencor and Biocytogen have collaborated on preclinical pharmacology studies, and Xencor moved forward with the new licensing agreement after Biocytogen released RenLite’s robust validation data.

"We are excited to begin this collaboration," said Dr. John Desjarlais, Xencor’s CSO. "We anticipate the RenMab and RenLite platforms will extend our bispecific antibody discovery and look forward to working with the team at Biocytogen."

The agreement, reached on October 27, includes licenses for the RenMab and RenLite mouse platforms and Biocytogen’s ongoing support of Xencor’s drug development efforts to help meet the increasing global demand for effective biologic therapies.

"We are delighted that Xencor has selected the Biocytogen RenMab/RenLite mice for their development of novel fully human antibody candidates," said YueLei Shen, Founder and CEO of Biocytogen. "We are highly confident that the combination of our fully-humanized mouse model and Xencor’s proven expertise in drug discovery and development will provide the ideal collaboration for the Xencor’s discovery of clinically-relevant antibodies."

The RenMab and RenLite antibody platforms are available for licensing to pharmaceutical and biotechnology partners seeking to streamline their antibody discovery workflow. For more information on RenMab and RenLite, visit View Source

On December 7, 2020 Bolt Biotherapeutics, Inc., a clinical-stage immuno-oncology company developing tumor-targeted therapies that leverage the power of the innate and adaptive immune systems, reported the publication of a manuscript in Nature Cancer highlighting the development and use of Boltbody Immune Stimulating Antibody Conjugates (ISACs) for the treatment of HER2-expressing tumors in preclinical models (Press release, Bolt Biotherapeutics, DEC 7, 2020, View Source [SID1234572384]).

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The paper, titled "Immune-stimulating antibody conjugates elicit robust myeloid activation and durable anti-tumor immunity," describes that Boltbody ISACs initiated tumor killing and antigen presentation by myeloid cells with subsequent T cell-mediated anti-tumor immunity. The data indicate that Boltbody ISACs activate the innate and adaptive immune systems, ultimately resulting in complete tumor regressions in multiple tumor models and durable anti-tumor immunity. ISAC-mediated immunological memory was not limited to the target antigen as ISAC-treated mice were protected from rechallenge with the parental tumor lacking HER2 expression. These results provide a strong rationale for the currently ongoing Phase 1/2, multi-center, open-label study of the company’s lead candidate, BDC-1001, and the continued development of the Boltbody ISAC technology platform and Bolt’s immuno-oncology pipeline.

Michael Alonso, Ph.D., scientific co-founder and vice president of immunology and pharmacology at Bolt, stated, "This publication lays the framework for therapeutic strategies that harness Boltbody ISACs and the profound biological synergies that occur following covalent attachment of an immunostimulant to a tumor-targeting antibody – notably, the complete elimination of well-established tumors and mobilization of T cells that prevent tumor recurrence."

Shelley Ackerman, Ph.D, lead author and co-inventor of the platform, said, "The publication of this peer-reviewed manuscript is an important milestone for Bolt with the first demonstration of the potential of our Boltbody ISAC platform. The data demonstrate the advantages achieved through requiring tumor target engagement, Fc receptor-mediated phagocytosis and subsequent TLR activation to induce a potent and localized anti-tumor response. This process effectively bridges the innate and adaptive immune systems to launch a coordinated anti-tumor response."

David Dornan, Ph.D., senior vice president of research and manufacturing at Bolt, added, "The work described is a culmination of years of experimentation and collaboration supported by our dedicated and talented team. This novel technology can be applied across a diverse range of tumor targets and has the potential to enable cancer patients to generate immunological memory against their own tumors. Our published data highlight the fact that while our Boltbody ISACs are administered systemically, the immune activation takes place where it is needed – in the tumor microenvironment. We look forward to reporting data from our ongoing Phase 1/2 clinical study assessing intravenous administration of our lead clinical molecule, BDC-1001, for the treatment of HER2-expressing tumors."

About Bolt Biotherapeutics’ Immune-Stimulating Antibody Conjugate (ISAC) Platform Technology
The Boltbody ISAC platform technology harnesses the ability of innate immune agonists to convert cold tumors into immunologically hot tumors, thereby illuminating tumors to the immune system and allowing them to be invaded by tumor killing cells. Boltbody ISACs have demonstrated the ability to eliminate tumors following systemic administration as monotherapy in preclinical models and have also led to the development of immunological memory, which is predicted to translate into more durable clinical responses for patients.

About the Ongoing BDC-1001 Phase 1/2 Study in Patients with HER2-Expressing Solid Tumors
The Phase 1/2, multi-center, open-label study is evaluating the safety, pharmacokinetics, pharmacodynamics and proof of mechanism of BDC-1001 in patients with HER2-expressing solid tumors. The first portion of the study includes a monotherapy dose-escalation phase in which cohorts of patients will receive ascending intravenous doses of BDC-1001 to determine the maximum tolerated dose and/or the recommended dose to advance into expansion cohorts and Phase 2 based on safety and tolerability. The second portion of the study is a dose expansion phase in which patients will receive BDC-1001 monotherapy to further evaluate the safety, tolerability and clinical antitumor activity of the recommended Phase 2 dose. Please refer to clinicaltrials.gov NCT04278144 for additional clinical trial information.

On December 7, 2020 Jubilant Therapeutics Inc., a biopharmaceutical company advancing small molecule modulators to address unmet medical needs in oncology and autoimmune diseases, reported efficacy data from a study of JBI-802, its novel dual inhibitor of LSD1-HDAC6, in multiple acute myeloid leukemia (AML) models, and the identification of novel, undisclosed biomarkers that will aid in patient stratification (Press release, Jubilant Therapeutics, DEC 7, 2020, View Source [SID1234572383]). The data, presented today in a poster session at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Virtual Annual Meeting, demonstrate superior efficacy in select AML models as compared to single agent inhibitors, with a unique mechanism of action.

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"We are highly encouraged to verify that both LSD1 and HDAC6 mechanisms are operational with JBI-802 and the dual inhibition shows a stronger and more potent effect than the standalone inhibitors. We are also excited about the potential biomarkers we have identified specifically for the dual inhibitor which will be highly valuable in identifying sensitive patient populations," said Syed Kazmi, President and Chief Executive Officer of Jubilant Therapeutics. "We believe JBI-802 could one day serve as a powerful therapeutic agent for the treatment of specific cancers, including myelodysplastic syndrome (MDS), select acute myeloid leukemia (AML) and solid tumor subsets."

A link to the abstract, Novel Dual Inhibitor of LSD1-HDAC6/8 for Treatment of Cancer, is available through the ASH (Free ASH Whitepaper) conference website.

Key highlights from the study of JBI-802 as compared to single agent LSD1 or HDAC6 selective inhibitors in AML models show:

Both LSD1 and HDAC6 mechanisms are operational with JBI-802 resulting in stronger anti-proliferation and efficacy in a subset of cell lines;
Selective biomarkers are modulated with the dual inhibition of JBI-802 not seen by the single agent inhibitors, leading to the potential for patient stratification and the evaluation of treatment response; and
JBI-802 has a superior efficacy, safety and tolerability profile.