On June 12, 2019 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported that the first patient has been dosed in a Phase 1/2 study evaluating the investigational agent TP-0903, an AXL receptor tyrosine kinase (RTK) inhibitor, in patients with previously treated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) (Press release, Tolero Pharmaceuticals, JUN 12, 2019, View Source [SID1234537051]). The open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study will evaluate the dose-limiting toxicities and clinical activity of oral TP-0903 administered in patients with previously treated CLL/SLL, as monotherapy or in combination with ibrutinib.

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"Although there have been significant advances in the treatment of CLL and SLL in recent years, there remains an area of clinical unmet need for patients who have had disease progression or relapse with available therapies." said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals. "The initiation of this study will allow us to learn more about the clinical profile of TP-0903 and the role of AXL receptor tyrosine kinase (RTK) inhibition in patients with previously treated CLL and SLL."

The primary outcome measures of the Phase 1 study are to determine dose-limiting toxicities and the incidence of treatment-emergent adverse events of oral TP-0903 administered once daily for 28 days in patients with previously treated CLL/SLL. Secondary outcome measures of the Phase 1 study include pharmacokinetics. The recommended Phase 2 dose (RP2D) will be determined in Phase 1 of the study. Phase 2 of the study will begin after the completion of Phase 1. The primary outcome measure of Phase 2 will be to determine the objective response rate according to guidelines set forth by the 2018 International Workshop on CLL. Secondary outcome measures of the Phase 2 study include assessment of duration of response and rate of overall survival.

In Phases 1 and 2 of the study, patients will be assigned to one of two defined patient groups. Patients in Group 1, which includes those who are intolerant to or have progressed on B-cell receptor antagonists and/or BCL-2 antagonists, will receive TP-0903 monotherapy. Patients in Group 2, which includes those who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient, will receive combination therapy of TP-0903 and ibrutinib. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at www.ClinicalTrials.gov (NCT03572634).

About TP-0903
TP-0903 is an investigational oral AXL receptor tyrosine kinase (RTK) inhibitor under evaluation in a Phase 1/2 study in patients with CLL/SLL (NCT03572634) and a Phase 1b study in patients with advanced solid tumors (NCT02729298). Tolero is exploring parallel clinical development paths for TP-0903 in both solid and hematologic malignancies.

About AXL Kinase
AXL belongs to the TAM (Tyro3, AXL and Mer) family of receptor tyrosine kinases and is overexpressed in many human cancers.1 It plays a key role in tumor cell proliferation, survival, metastasis, cellular adhesion and avoidance of the immune response. The overexpression of AXL is associated with a poor patient prognosis and drug resistance.2

On June 12, 2019 Dr. Reddy’s Laboratories Ltd (BSE:500124, NSE: DRREDDY, NYSE: RDY) reported that the Company will be presenting at the Goldman Sachs 40th Annual Global Healthcare Conference on Wednesday, June 12th, 2019, in California (Press release, Dr Reddy’s, JUN 12, 2019, View Source [SID1234537036]).

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Marc Kikuchi, CEO, North America Generics will present at Fireside Chat session at 2:00 p.m. PST [2:30 a.m. IST on June 13th, 2019].

Presentation material will be available on the Company’s website www.drreddys.com

On June 12, 2019 GlaxoSmithKline plc reported new data on belantamab mafodotin (GSK2857916), an investigational anti-B-cell maturation antigen (BCMA) antibody-drug conjugate, will be presented at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) (Press release, GlaxoSmithKline, JUN 12, 2019, View Source [SID1234537037]).

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The studies being presented at EHA (Free EHA Whitepaper) include:

Abstract #PS1401: Patient Reported Experience from Part 2 of the First Time in Human Study of the BCMA Antibody-Drug Conjugate GSK2857916 for Advanced Relapsed Refractory Multiple Myeloma (DREAMM-1) (Popat R, Opalinska L, Eliason J, et. al)
Abstract #PS1372: B-cell Maturation Antigen Antibody-Drug Conjugate (ADC), GSK2857916, in Relapsed/Refractory Multiple Myeloma (RRMM): Final Safety, Efficacy and Pharmacokinetic (PK) Analyses From a Pivotal Phase I Study (Popat R, Lendvai S, Trudel PM, et. al)
Abstract #PF558: The Anti-BCMA Antibody-Drug Conjugate GSK2857916 Drives Immunogenic Cell Death and Immune-Mediated Anti-Tumor Responses, and in Combination with an OX40 Agonist Potentiates in Vivo Activity (Montes De Oca R, Bhattacharya S, Vitali N, et. al)
In 2017, belantamab mafodotin was awarded Breakthrough Therapy designation from the U.S. Food and Drug Administration and PRIME designation from the European Medicines Agency; these designations are intended to facilitate development of investigational medicines that have shown clinical promise for conditions where there is significant unmet need.

About B-cell maturation antigen (BCMA)

The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF and APRIL. This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines[i].

About the DREAMM Clinical Trial Programme for Belantamab Mafodotin (GSK2857916)

Belantamab mafodotin is an antibody-drug conjugate comprising a humanised anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker. The drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using technology licensed from BioWa.

Belantamab mafodotin is currently in clinical development in patients with relapsed/refractory multiple myeloma and other advanced haematologic malignancies expressing BCMA.

Belantamab mafodotin is not currently approved for use anywhere in the world.

GSK in Oncology

GSK is focused on maximizing patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On June 12, 2019 NuCana plc (NASDAQ: NCNA) reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for the Company’s investigational drug, Acelarin (NUC-1031), for the treatment of biliary tract cancer (Press release, Nucana BioPharmaceuticals, JUN 12, 2019, View Source [SID1234537054]). Acelarin is a new chemical entity and is NuCana’s ProTide transformation of gemcitabine.

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"We are pleased to have received orphan drug designation from the FDA for Acelarin in biliary tract cancer," said Hugh Griffith, NuCana’s Founder and Chief Executive Officer. "There is a high unmet need for patients suffering from this cancer type. Our Phase Ib study of Acelarin combined with cisplatin showed an approximate doubling of the response rate expected with the standard of care, gemcitabine plus cisplatin, with several patients achieving significant reductions in their tumor volume as well as further tumor shrinkage over time. We believe Acelarin represents a potential significant advance in biliary tract cancer and we remain on track to open our global Phase III study in combination with cisplatin as a front-line treatment for patients with advanced biliary tract cancer in 2019."

Orphan drug designation is granted by the FDA to drugs that are defined as those intended for the treatment, prevention or diagnosis of rare diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug designation provides certain benefits and incentives that may include tax credits towards the cost of clinical trials and prescription drug user fee waivers.

About Biliary Tract Cancer

Biliary tract cancer is a form of cancer that develops in the bile duct system, which connects the liver, gallbladder, and small intestine, moving bile – a fluid that helps digest fats – to the small intestine. Approximately 178,000 new cases of biliary tract cancer are diagnosed each year worldwide, with more than 12,000 of those diagnoses in the United States.

On June 12, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage immuno-oncology corporation, reported updated data from the ongoing investigator-sponsored SPiReL Phase 2 clinical trial assessing IMV’s lead candidate, DPX-Survivac, in combination with intermittent low dose cyclophosphamide and Merck’s checkpoint inhibitor Keytruda (pembrolizumab) (Press release, IMV, JUN 12, 2019, View Source [SID1234537038]). The trial is designed to evaluate the safety and efficacy of the combination immunotherapy in patients with persistent or recurrent/refractory diffuse large B-cell lymphoma (DLBCL).

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At the first "on treatment" assessment, five of the first six patients demonstrated clinical benefit, including four patients with tumor regressions. Two patients reached a complete radiological response, one a partial response, and two had stable disease while on study. In addition, the combination continued to demonstrate an acceptable safety profile.

"We are highly encouraged by the level of activity that we are observing with the combination of DPX-Survivac and Keytruda in these patients with DLBCL," said Frederic Ors, IMV’s Chief Executive Officer. "We believe that the clinical benefits the SPiReL trial has yielded thus far, and the data linking this antitumor activity with the T cell responses, support DPX-Survivac’s novel mechanism of action and our combination immunotherapy approach. We will continue working with our partners to advance this clinical study towards improving the lives of patients with difficult-to-treat cancers who need better treatment options."

Updated SPiReL Data Highlights:

At the time of data cut-off for this analysis, 11 patients were enrolled in the trial. Efficacy data from the first six evaluable patients are based on modified Cheson criteriai:

Two patients achieved a complete radiological response

These patients have shown the best survivin specific T cell responses to DPX- Survivac among the analyzed samples

One patient with a Complete Response (CR) has completed the one-year study period

One patient achieved a Partial Response (PR) at first "on treatment" scan

Two patients have reached stable disease

i Cheson, B.D.,, Pfistner, B., Juweid, M.E., Gascoyne, R.D., Specht, L., Horning, S.J., . . . and Diehl, V. (2007). Revised Response Criteria for Malignant Lymphoma. Journal of Clinical Oncology, 25(5) DOI: 10.1200/JCO.2006.09.2403

Each of these patients has remained progression free for six and eight months while on treatment

One patient with bulky disease progressed at first scan

Two subjects are not evaluable, coming off trial at day 7 and day 28

The treatment combination appears to be well-tolerated with only 2 serious adverse events related to treatment (low white blood count and low neutrophil count)

Radiological results from three additional patients are pending

The ICML abstract was published on June 12, 2019 via the 15-ICML ABSTRACT BOOK, a supplement to Hematological Oncology with first author Neil Berinstein, MD, FRCPC, ABIM Haematologist at the Odette Cancer Centre, Sunnybrook Health Sciences Centre and Affiliate Scientist at Sunnybrook Research Institute. Dr. Berinstein will be available at the ICML conference to discuss the results.

IMV will host a conference call and webcast to discuss the SPIREL results today, Wednesday, June 12, 2019, at 8:00 a.m. ET. Financial analysts are invited to join the conference call by dialing (866) 211-3204 (U.S. and Canada) or (647) 689-6600 (International) using the conference ID: 9685423. Other interested parties will be able to access the live audio webcast at this link: View Source The webcast will be recorded and made available on the IMV website for 30 days following the call.

About DLBCL

Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of malignant lymphoma worldwide and accounts for approximately one third of all non-Hodgkin lymphomas. In the United States, it is estimated that nearly 25,000 new cases of DLBCL will be diagnosed in 2019. As many as 30% of all patients with DLBCL who either fail to respond to or show a relapse to initial therapies are reported to have a poor outcome and require more therapeutic options.

About the SPiReL Study

SPiReL (DPX-Survivac with Low Dose Cyclophosphamide administered with Pembrolizumab in Patients with persistent or Recurrent/refractory Diffuse Large B-Cell Lymphoma) is a Phase 2 non-randomized, multi-centre, open-label study. Primary Investigator Dr. Neil Berinstein is leading the trial, which is expected to enroll 25 evaluable participants whose recurrent DLBCL expresses survivin, a tumor antigen expressed in of the majority of DLBCL tumors. The study’s primary endpoint is to document the objective response rate. Secondary objectives include measuring tumor regression and documenting the toxicity profile and durations of response. In addition, investigators will perform analyses to assess circulating antigen specific immune responses and changes in tumor-infiltrating T cell immune responses within the tumor microenvironment. They also plan to assess potential biomarkers of immune and clinical response.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapies that programs targeted T cells in vivo. It has demonstrated the potential for industry-leading targeted, persistent, and durable T cell activation. IMV believes this mechanism of action (MOA) is key to generating durable solid tumor regressions. DPX-Survivac consists of survivin-based peptides formulated in IMV’s proprietary DPX drug delivery platform. DPX-Survivac is designed to work by eliciting a

cytotoxic T cell immune response against cancer cells presenting survivin peptides on their surface.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to anti-cancer therapies. IMV has identified over 15 cancer indications in which the over-expression of survivin can be targeted by DPX-Survivac.

The U.S. Food and Drug Administration (FDA) has provided Fast Track designation to DPX-Survivac as maintenance therapy in advanced ovarian cancer. In addition, the FDA and European Medicines Agency (EMA) have granted orphan drug designation status in the ovarian cancer indication. Investigators are currently evaluating DPX-Survivac in multiple Phase 2 clinical trials.