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.

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"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.

On December 14, 2018 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported safety and promising activity of BPX-601 in Part 1 of a Phase 1/2 dose-escalation study in patients with advanced, metastatic pancreatic cancer expressing PSCA (prostate stem cell antigen) (Press release, Bellicum Pharmaceuticals, DEC 14, 2018, View Source [SID1234532061]). BPX-601 is a novel GoCAR-T cell candidate incorporating Bellicum’s co-activation domain, iMC, designed to boost T cell proliferation and persistence via administration of rimiducid. Data were reviewed during an oral presentation at the European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO) held in Geneva, Switzerland from December 13-16.

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"These initial results in advanced pancreatic cancer suggest that having greater control over the expansion and persistence of therapeutic cells may provide unique treatment benefits. We have observed promising initial clinical activity with BPX-601 in patients with one of the most challenging solid tumors, where there is a critical need for better treatments," commented Carlos R. Becerra, M.D., lead study investigator and oncologist and medical director of the Innovative Clinical Trials Center at Baylor University Medical Center at Dallas. "I am looking forward to the next phase of our study, which allows for a standard lymphodepletion regimen and administration of multiple doses of rimiducid to further increase the expansion and persistence of BPX-601 cells and the potential for greater impact against pancreatic and other tumor types."

Study Overview
A total of 12 patients with advanced metastatic pancreatic cancer expressing PSCA were treated with escalating doses of BPX-601 cells in a 3+3 design. Nine of 12 patients received a single dose of rimiducid following BPX-601 treatment to evaluate its effect on cell expansion and persistence. Patients in the study received a reduced conditioning regimen consisting of cyclophosphamide only.

Interim Results:

The administration of BPX-601 without rimiducid resulted in limited expansion of cells, but the cells did not persist; A single dose of rimiducid 7 days following BPX-601 administration resulted in significant expansion of cells (three-fold to 20-fold) in four patients in spite of a reduced conditioning regimen; BPX-601 cells persisted longer than three weeks in three patients after a single dose of rimiducid; Increases in key cytokine levels were observed in patients receiving higher doses of BPX-601 cells and rimiducid; 4 of 6 efficacy-evaluable patients treated with BPX-601 and a single dose of rimiducid had stable disease, with two patients demonstrating tumor shrinkage greater than 20 percent; No cytokine release syndrome or neurotoxicity of any grade was reported; The most frequently observed AEs were consistent with those experienced by advanced cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies; Patients continue to be evaluated in the study.
"These results provide the first clinical evidence suggesting that our GoCAR-T technology drives expansion and persistence of therapeutic T cells in patients," said Rick Fair, President & CEO of Bellicum Pharmaceuticals. "We are excited about BPX-601 and the broader application of our technology intended to improve the safety and efficacy of cell therapies. With these promising results, we’re preparing to begin Part 2 of the BPX-601 study, adding patients with prostate and gastric cancers, allowing multiple doses of rimiducid and a more complete conditioning regimen. We’re looking forward to reporting updated results in 2019."

About BPX-601
BPX-601, the Company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence, and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for solid tumors expressing prostate stem cell antigen (PSCA), including pancreatic, prostate and gastric cancers.

On December 14, 2018 Pfizer Inc. (NYSE:PFE) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending marketing authorization for ZIRABEV (bevacizumab), a potential biosimilar to Avastin (bevacizumab) (Press release, Pfizer, DEC 14, 2018, View Source [SID1234532063]).1 ZIRABEV is a monoclonal antibody for the treatment of metastatic carcinoma of the colon or rectum, metastatic breast cancer, unresectable advanced, metastatic or recurrent non-small cell lung cancer (NSCLC), advanced and/or metastatic renal cell cancer and persistent, recurrent or metastatic carcinoma of the cervix.2

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"If approved, ZIRABEV has the potential to expand access to this life-changing biologic cancer therapy for appropriate patients and healthcare professionals across Europe," said Joe McClellan, Vice President, Biosimilars Development at Pfizer. "Today’s positive CHMP opinion underscores Pfizer’s strong heritage in oncology and its ongoing commitment to bringing high-quality biosimilars to market, providing additional options for people living with certain cancers."

The regulatory submission is supported with a comprehensive data package and evidence demonstrating biosimilarity to the originator product. This includes results from the phase 3 REFLECTIONS B739-03 clinical comparative study, which demonstrated clinical equivalence and found no clinically meaningful differences between ZIRABEV and Avastin in patients with advanced non-squamous NSCLC.3 As part of the overall REFLECTIONS clinical trial program, ZIRABEV has been studied in approximately 400 subjects.3,4

ZIRABEV is Pfizer’s second therapeutic oncology biosimilar to receive a positive CHMP opinion from the EMA in 2018.5 Pfizer has a robust portfolio of potential biosimilar candidates in mid to late stage development and we are confident about our ability to bring these important medicines to the patients who need them around the world.6

On December 14, 2018 Idera Pharmaceuticals, Inc. (NASDAQ: IDRA) reported is presenting data from the ongoing phase 2 expansion of the ILLUMINATE-204 trial investigating tilsotolimod, Idera’s intratumorally-delivered toll-like receptor 9 (TLR9) agonist, in combination with ipilimumab (Yervoy*) (Press release, Idera Pharmaceuticals, DEC 14, 2018, View Source [SID1234532066]).

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ILLUMINATE-204 Key Findings:

37 patients dosed with 8 mg of tilsotolimod in combination with ipilimumab were evaluated for this update:
34 patients were evaluable for efficacy
All patients were evaluable for safety
Accrual is ongoing, with an additional 4 patients dosed
Responses, including 2 Complete Responses (CR), were observed in 11 of the 34 evaluable patients (32.4%)
Duration of response ranges from > 1 month to > 30 months, with 36% of responses ongoing
Per RECIST v1.1, the Overall Response Rate (ORR) is 29.4%; one patient with an unconfirmed Partial Response (uPR) at the end of treatment assessment progressed due to a new lesion at the 3-month follow-up disease assessment
Overall, 26 patients out of 34 evaluable for efficacy (76.5%) experienced disease control (CR, PR, or Stable Disease (SD))
Analysis of spider plots show tumor shrinkage in both injected and uninjected lesions, indicating an abscopal effect
Responding subjects include one patient with mucosal melanoma and one patient with acral melanoma, two forms of melanoma that are particularly difficult to treat
Importantly, 2 of 5 patients with prior ipilimumab experience achieved responses, further demonstrating a signal that tilsotolimod has the potential to help overcome prior ipilimumab resistance
The combination regimen continues to be generally well tolerated. 9/37 subjects (24.3%) had immune-related toxicities indicating that tilsotolimod + ipilimumab does not appear to add immune-related toxicity versus ipilimumab alone
Injection-related toxicities were grade 1-2 transient fever and flu-like symptoms lasting <48 hours
Additionally:

A RECIST v1.1 PR of > 2.5 years is ongoing in 1 patient treated with tilsotolimod 4 mg in combination with ipilimumab; and
A RECIST v1.1 CR of > 1 year is ongoing in 1 patient treated with tilsotolimod 16 mg in combination with pembrolizumab.
"The results from this combination are among the most promising we have seen in this challenging population of metastatic melanoma patients who have not benefited from front-line immunotherapy," stated Douglas B. Johnson, M.D., Assistant Professor of Medicine, Clinical Director, Melanoma Research Program, Vanderbilt University Medical Center. "In addition to the response rate, observing over 76% of patients achieving disease control is impressive for such a difficult-to-treat patient population."

The ILLUMINATE-204 trial is comprised of two distinct patient populations, patients who are ipilimumab naïve (N=up to 40; Primary Efficacy Endpoint Population) and patients who have ipilimumab experience (N=up to 20; Secondary Efficacy Endpoint Population). Of the initial 34 patients evaluable for efficacy, evaluations 9 of 29 patients from the Primary Efficacy Endpoint Population and 2 of 5 patients from the Secondary Efficacy Endpoint Population achieved responses.

Indications of the specific mechanism of action for tilsotolimod were suggested in the clinical responses observed in patients whose tumor HLA-ABC RNA (MHC class I) expression was low at baseline. As recently articulated by Rodig, et al.1 robust MHC class I expression is required for anti-CTLA-4 activity. These findings suggest that combining tilsotolimod with ipilimumab may overcome this resistance mechanism and, therefore, enhance the overall response rate compared to that expected with ipilimumab alone.

"The continued positive results from this trial, a response rate substantially higher than expected with ipilimumab alone, and anti-tumor activity in both injected and uninjected lesions are exciting. These reinforce our conviction that tilsotolimod may overcome an immunosuppressive tumor microenvironment and, in combination with ipilimumab, could provide a treatment option when anti PD-1 therapy fails these patients," stated Dr. Joanna Horobin, Idera’s Chief Medical Officer. "These data, along with the translational data, bolster our confidence in both the Phase 3 trial and taking tilsotolimod beyond melanoma."

Investor Event and Webcast
Idera will host a conference call and live webcast today, Friday, December 14, at 10:00 A.M. EST to review the data being presented along with questions and answers. To participate in the conference call, please dial (844) 882-7837 (domestic) and (574) 990-9824 (international). The webcast can be accessed live or in archived form in the "Investors" section of the company’s website at www.iderapharma.com. The company has posted a slide presentation to the Idera corporate website in the "Investors" section which will be referenced during the conference call this morning.

About Tilsotolimod (IMO-2125)
Tilsotolimod is a TLR 9 agonist that received Fast Track Designation from the US Food and Drug Administration (FDA) in 2017 for the treatment of anti-PD-1 refractory melanoma, in combination with ipilimumab as well as orphan drug designation from the FDA for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors. Currently approved immuno-oncology treatments, specifically check-point inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy. Intratumoral injections with tilsotolimod are designed to selectively enable the tumor-specific T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.

About ILLUMINATE-204
The ILLUMINATE-204 study (2125-204) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda** (pembrolizumab) or Opdivo* (nivolumab) has failed. ILLUMINATE-204 is a multi-center, two-arm Phase 1/2 study that tests the safety and effectiveness of tilsotolimod in combination with either ipilimumab (Yervoy) or pembrolizumab (Keytruda) for the treatment of patients with anti-PD-1 refractory metastatic melanoma.

For additional details about ILLUMINATE-204, please go to clinicaltrials.gov and search for study identifier NCT02644967.

About Metastatic Melanoma
Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths. The American Cancer Society estimates that there were approximately 76,000 new invasive melanoma cases and 10,000 deaths from the disease in the USA in 2016. Additionally, according to the World Health Organization, about 132,000 new cases of melanoma are diagnosed around the world every year.

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]).

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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.