1stOncology™: Cancer Intelligence Service – Page 14366 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Atara Biotherapeutics Presents Positive Efficacy and Safety Results for Patients with Epstein-Barr Virus-Associated Leiomyosarcoma (EBV+ LMS)

On December 15, 2018 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported its results indicating that tab-cel (tabelecleucel) was generally well tolerated with responses for patients with Epstein-Barr virus-associated leiomyosarcoma (EBV+ LMS) (Press release, Atara Biotherapeutics, DEC 15, 2018, View Source [SID1234532076]). EBV+ LMS is a rare soft tissue sarcoma that occurs in transplant and immunosuppressed patients and is typically an aggressive radiation- and chemotherapy-resistant disease with poor patient outcomes. The results were presented in an oral session at the European Society for Medical Oncology Immuno-Oncology (ESMO I‑O) Congress 2018 taking place in Geneva, Switzerland.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"The EBV+ LMS results presented at ESMO (Free ESMO Whitepaper) I-O are the second example, along with nasopharyngeal carcinoma (NPC), of a difficult-to-treat, EBV-associated solid tumor with encouraging responses to tab‑cel," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "Observations of responses based on standard-CT and metabolic PET-CT imaging, in the context of prolonged survival, further highlight the opportunity for tab‑cel and off-the-shelf, allogeneic T-cell immunotherapy in EBV-associated cancers beyond our ongoing studies for patients with post‑transplant lymphoproliferative disease (PTLD) and NPC."

The oral presentation summarized the evaluation of tab-cel in an analysis of EBV+ LMS patients from three clinical studies, 2 single-center, open-label studies (NCT00002663, NCT01498484) and the multi‑center expanded access protocol (EAP) study (NCT02822495). Twelve patients with EBV+ LMS received one or more doses of tab-cel, of whom 10 were assessed for responses with two patients not evaluable. Two of the 10 patients achieved a partial response via CT-based RECIST 1.1 criteria and eight patients achieved stable disease. In the two single-center studies with longer follow-up, six of eight patients survived more than 27 months and the estimated median survival was 77.4 months. At the time of this analysis, responses assessed by PET-CT imaging were available from the multi-center EAP study where 3 of the 4 patients achieved a metabolic response. Tab-cel was generally well tolerated and the safety appeared consistent with a favorable risk profile and previous clinical studies.

About tab-cel (tabelecleucel)
Atara’s most advanced T-cell immunotherapy in development, tab-cel, is a potential treatment for patients with Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (EBV+ PTLD) who have failed rituximab, as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, the FDA granted tab-cel Breakthrough Therapy Designation for EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tab-cel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. In addition, tab-cel has orphan status in the U.S. and EU. Tab-cel is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study), and Atara recently initiated a Phase 1/2 study in NPC.

BeiGene Announces Updated Phase 1A/1B Data on Tislelizumab Presented at the European Society for Medical Oncology Immuno-Oncology Congress

On December 15, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that updated clinical data from an ongoing Phase 1A/1B trial of tislelizumab, an investigational anti-PD-1 antibody, were presented in an oral session and a poster at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress, being held December 13-16 in Geneva, Switzerland (Press release, BeiGene, DEC 15, 2018, View Source;p=RssLanding&cat=news&id=2380786 [SID1234532073]).

"We continue to be pleased with the results of tislelizumab in solid tumors," commented Amy Peterson, M.D., Chief Medical Officer, Immuno-Oncology, at BeiGene. "We believe that these updated results provide support for the continued development of tislelizumab in patients with bladder, esophageal, stomach, liver and non-small cell lung cancers, and we have registration-enabling studies ongoing or planned to start soon in each of these indications."

Summary of ESMO (Free ESMO Whitepaper)-IO Presentations from the Ongoing Phase 1A/1B Trial
The multi-center, open-label Phase 1A/1B trial (NCT02407990) of tislelizumab as monotherapy in advanced solid tumors is being conducted in Australia, New Zealand, the United States, Taiwan and South Korea and consists of dose-escalation and dose-expansion phases in disease-specific cohorts.

Updated Results in Patients with Urothelial Carcinoma (UC)
Data presented at ESMO (Free ESMO Whitepaper)-IO included updated results from an analysis of tislelizumab in 17 patients with UC. At the time of the data cutoff on August 31, 2018, median treatment duration was 4.1 months (0.7-30.4 months), with two patients still on treatment.

Treatment-related adverse events (TRAEs) as assessed by the investigator occurred in 15 patients (88.2%). Of those, fatigue (n=5), infusion-related reactions (n=3), rash (n=3), nausea (n=2), pain in extremity (n=2), peripheral adema (n=2), and proteinuria (n=2) occurred in two or more patients. Three treatment-related Grade 3 or 4 AEs occurred in two patients, fatigue (n=1), and hyperglycemia and latent autoimmune diabetes (n=1). One patient discontinued treatment due to recurrent infusion-related reactions considered related to tislelizumab.

At the time of the data cutoff, all 17 patients were evaluable for response, defined as having a baseline tumor assessment with at least one post-baseline tumor response assessment, or progression or death. The confirmed response rate was 29.4 percent, with one complete response (CR) and four partial responses (PR). Three additional patients achieved stable disease (SD) as their best response. There was one CR, one PR and one SD among the eight patients with PD-L1 high tumors and two PRs and two SDs among the eight patients with PD-L1 low or negative tumors (one tumor was not-evaluable for PD-L1 expression). The median duration of response was 18.7 months (6.2-18.7 months).

Updated Results in Patients with Esophogeal, Gastric, Hepatocellular and Non-Small Cell Lung Cancers
In an oral presentation at ESMO (Free ESMO Whitepaper)-IO, data on patients with esophageal (EC, n=54), gastric (GC, n=54), hepatocellular (HC, n=50) and non-small cell lung cancers (NSCLC, n=49) were reported.

TRAEs occurring in at least five percent of patients across all cohorts included fatigue (8.7%), pruritis (7.7%), hypothyroidism (7.2%), decreased appetite (6.8%), rash (6.8%) and nausea (6.3%). Ten patients experienced one or more serious adverse events considered related to tislelizumab, including pneumonitis (n=3) and one case each of acute hepatitis, dermatitis, diarrhea, increased ALT, increased AST, infusion-related reaction, pyrexia and vomiting. Grade 3 or 4 TRAEs occurring in more than one patient included increased AST (n=4), increased ALT (n=3) and pneumonitis (n=2). There were two fatal TRAEs reported, including acute hepatitis in a patient with HCC confounded by rapidly progressive disease, and pneumonitis in a patient with NSCLC with compromised pulmonary capacity at baseline.

Confirmed response rates and disease control rates in patients with EC were 11.1 percent and 37.0 percent, respectively; 13.0 percent and 29.6 percent in patients with GC, respectively; 12.2 percent and 51.0 percent in patients with HCC, respectively, and 13.0 percent and 63.0 percent in patients with NSCLC, respectively. For patients with EC and NSCLC, the median duration of response (mDOR) had not been reached. The mDOR in patients with GC was 8.5 months and for patients with HCC it was 15.7 months.

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

Discovered by BeiGene scientists, tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. The new drug application (NDA) for tislelizumab in China for patients with relapsed/refractory (R/R) classical Hodgkin’s lymphoma (cHL) has been accepted by the China National Medical Products Administration (NMPA, formerly known as CFDA) and granted priority review status. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumors in the United States, Europe, Japan and the rest of world outside Asia.

Helix BioPharma Corp. Announces Fiscal First Quarter 2019 Results

On December 14, 2019 Helix BioPharma Corp. (TSX, FSE: "HBP"), a an immuno-oncology company developing drug candidates for the prevention and treatment of cancer, reported its financial results for the first quarter of fiscal 2019 ending October 31, 2018 (Press release, Helix BioPharma, DEC 14, 2018, View Source [SID1234533058]).

FINANCIAL REVIEW

The Company recorded a net loss and total comprehensive loss of $1,379,000 ($0.01 loss per common share) and $2,303,000 ($0.02 loss per common share) for the three-month periods ended October 31, 2018 and 2017, respectively. Due to Helix’s cash constraints, the Company has proactively had to manage its limited cash resources which has resulted in an overall reduction in spending and in turn delays to its clinical development programs.

Research and development

Research and development costs for the three-month periods ended October 31, 2018 and 2017 totalled $1,014,000 and $1,764,000, respectively.

L-DOS47 research and development expenses for the three-month periods ended October 31, 2018 and 2017 totalled $861,000 and $1,482,000, respectively. L-DOS47 research and development expenditures relate primarily to the Company’s LDOS002 European Phase I/II clinical study in Poland and the LDOS001 U.S. Phase I clinical study in the U.S in addition to some preliminary expenditures related to the Company’s LDOS003 Phase II clinical study in Poland and Ukraine. The lower LDOS47 spending is mainly the result of the winding down of the Company’s LDOS002 European Phase I/II clinical study in Poland. Given the limited cash resources, the Company had slowed down the previously committed LDOS003 clinical trial. The Company has recently advanced the funds to the CRO for the commencement of enrollment which is now underway. The Company continues to be committed to the LDOS001 study and has re-allocated resources to improve patient enrollment. The Company has begun early development of a Phase I/II study, L-DOS47 given in combination with doxorubicin, for the treatment of metastatic pancreatic cancer. An initial draft study protocol was circulated in July 2018 and ongoing development continues.

V-DOS47 research and development expenses for the three-month periods ended October 31, 2018 and 2017 totalled $130,000 and $113,000, respectively. The Company’s wholly owned subsidiary in Poland has a grant funding agreement with the Polish National Centre for Research and Development ("PNCRD") for research and development expenditures associated with V-DOS47. The Company’s subsidiary received $135,000 and $83,000 in the three-month periods ended October 31, 2018 and 2017, respectively, from the PNCRD. The Company is looking at the possibility of selling its Polish subsidiary to raise capital in order to fund its L-DOS47 program and deal with its working capital deficiency.

Trademark and patent related expenses for the three-month periods ended October 31, 2018 and 2017 totalled $25,000 and $99,000, respectively. The Company previous had committed spend in order to adequately protect the Company’s intellectual property.

Operating, general and administration

Operating, general and administration expenses for the three-month periods ended October 31, 2018 and 2017 totalled $373,000 and $526,000, respectively. The decrease in operating, general and administration expenses mainly reflects ongoing cost cutting initiatives.

LIQUIDITY AND CAPITAL RESOURCES

The Company reported a consolidated net loss and total comprehensive loss of $1,379,000 for the three-month period ended October 31, 2018 (October 31, 2017 – $2,303,000). As at October 31, 2018 the Company had a working capital deficiency of $1,997,000, shareholders’ deficiency of $1,651,000 and a deficit of $165,384,000. As at July 31, 2018 the Company had a working capital deficiency of $1,901,000, shareholders’ deficiency of $1,527,000 and a deficit of $164,005,000.

The Company continues to work with vendors to manage its cash position while ensuring vendors continue providing services while being paid, albeit over a longer period of time than previously agreed terms. The Company has raised gross proceeds of approximately $8,518,000 from private placement financings during fiscal 2018 and an additional $1,616,000 in the current quarter, the Company’s cash reserves of $871,000 as at October 31, 2018 in addition to the subsequent private placements the Company closed on October 30, 2018 for gross proceeds of approximately $871,000 are insufficient to meet anticipated cash needs for working capital and capital expenditures through the next twelve months, nor are they sufficient to see the current or any planned research and development initiatives through to completion. Though the funds raised have somewhat assisted the Company in dealing with its working capital deficiency and attempts to make vendors current, additional funds are required to advance the various clinical and preclinical programs, pay for the Company’s overhead costs and its past due vendors. To the extent that the Company does not believe it has sufficient liquidity to meet its current obligations, management considers securing additional funds, primarily through the issuance of equity securities of the Company, to be critical for its development needs. The Company is looking at the possibility of selling its Polish subsidiary to raise capital in order to fund its L-DOS47 program and deal with its working capital deficiency.

RadioMedix presented at the 2018 BIO Investor Forum in San Francisco

On December 14, 2018 RadioMedix Inc reported that it has been selected by the National Cancer Institute (NCI) Small Business Innovation Research Development Center (SBIR) to participate in 2018 BIO Investor Forum (Press release, RadioMedix, DEC 14, 2018, View Source [SID1234532131]). The company received federal funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services (HHSN261201600015C, HHS261201800048C/75N91018C00048) for the development of radiotherapeutic alpha-emitter labeled agents.

Dr. Izabela Tworowska, Chief Science Officer of RadioMedix, presented an overview of the company pipeline, the financial growth of RadioMedix, and status of the clinical development of radiotheranostic drugs. The presentation was sponsored by NCI SBIR Development Center’s Investor Initiatives program.

"We have been invited to attend the BIO Investor Forum in San Francisco for two consecutive years and we are grateful to the NCI SBIR Investor Initiatives for this invitation ", said Dr. Tworowska. "It is a great opportunity to attend BIO One-on-One Partnering meetings, discuss the future goals of our company and gain the interest of investors and business partners", added Dr. Tworowska.

"RadioMedix’s rich clinical stage pipeline of innovative radiopharmaceuticals makes an attractive case for investors, and large companies, familiar with our space", said Dr. Delpassand, Chairman and CEO of RadioMedix. "Targeted radioligand therapy will be the strongest segment in the field of nuclear medicine and RadioMedix is well-positioned to take advantage of this opportunity", added Dr. Delpassand.

Glenmark Pharmaceuticals Announces New Data on GBR 1302, a HER2xCD3 Bispecific Antibody, Presented at the ESMO Immuno-Oncology Congress 2018

On December 14, 2018 Glenmark Pharmaceuticals, a global innovative pharmaceutical company, reported the presentation of new pharmacokinetic data from the ongoing Phase 1 trial of GBR 1302, a HER2xCD3 bispecific antibody, at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress 2018 in Geneva, Switzerland (Press release, Glenmark, DEC 14, 2018, View Source [SID1234532079]). GBR 1302 is Glenmark’s lead immuno-oncology candidate and is currently in a first-in-human trial to determine maximum tolerated dose (MTD) in an all-comers population of patients with a variety of HER2 positive cancers. These Phase 1 data will inform dosing regimen optimization of GBR 1302.

"Due to the anticipated potency and limited clinical experience with T-cell redirecting bispecific antibodies, determining the optimal dosing regimen for novel investigational medicines like GBR 1302 is key to unlocking its potential," said Mahboob Rahman, President and Chief Medical Officer at Glenmark Pharmaceuticals. "An innovative method of quantification was developed to facilitate the measurement of very low systemic concentrations of GBR 1302 in the clinical study. These findings provide insights into the pharmacokinetics of GBR 1302 and inform dosing regimen decisions to maximize its potential effectiveness for patients with HER2 positive cancers."

A low starting dose of 1 ng/kg was selected for the first-in-human Phase 1 study of GBR 1302, and dose escalation continued in small increments using a biweekly regimen. Glenmark developed and utilized a novel hybrid immunocapture-LC/MS/MS method for quantification of GBR 1302 in human serum to overcome the difficulty of generating pharmacokinetic data at the low doses administered in the study.1

Pharmacokinetic profiles of GBR 1302 were observed from doses of 30 ng/kg and beyond. In general, maximum concentration (Cmax) was observed close to the end of infusion, after which serum concentrations declined bi-exponentially, with a mean terminal half-life of approximately four to seven days. Both, Cmax and exposure (AUC0-t), showed near dose-proportional increases up to 750 ng/kg, the highest dose evaluated in the Phase 1 trial thus far.1

Consistent with the half-life findings, Glenmark plans to initiate a study of GBR 1302 in HER2 positive breast cancer patients with a weekly dosing regimen.

About Glenmark’s Oncology Pipeline and Proprietary BEAT Technology
Glenmark’s pipeline currently includes three immuno-oncology candidates being studied in a wide range of tumor types. These include three bispecific monoclonal antibodies (bsAbs). GBR 1302, a HER2xCD3 bsAb, targets HER2 expressing tumors including those not responsive to standard of care; GBR 1342, a CD38XCD3 bsAb targeting CD38 positive tumors including hematologic malignancies and solid tumors; and GBR 1372, an EGFRxCD3 bsAb targeting EGFR positive tumors including those resistant to standard of care.

BEAT (Bispecific Engagement by Antibodies based on the T cell receptor) is Glenmark’s proprietary technology for the production of bsAbs. With BEAT technology, Glenmark’s scientists have been able to overcome past production obstacles encountered with bsAbs and can efficiently manufacture these molecules at clinical and commercial scale. Preclinically, BEAT bsAbs demonstrate the potential for more potent activity compared to existing therapeutic antibodies. Additionally, structural similarity to naturally-occurring antibodies may result in a normalized IgG half-life and less immunogenicity. GBR 1302, GBR 1342 and GBR 1372 are based on BEAT technology.