On December 16, 2018 Innovent Biologics, Inc. (Innovent) (HKEX: 01801) and Incyte (NASDAQ:INCY) reported that the companies, through their respective subsidiaries, have entered into a strategic collaboration agreement for three clinical-stage product candidates discovered and developed by Incyte—pemigatinib (FGFR1/2/3 inhibitor), itacitinib (JAK1 inhibitor) and parsaclisib (PI3Kδ inhibitor) (Press release, Incyte, DEC 16, 2018, View Source [SID1234532118]). Under the terms of the agreement, Innovent will pay Incyte US$40 million in cash up front, and Incyte shall be eligible to receive an additional US$20 million in consideration in connection with the first investigational new drug (IND) application by Innovent in China, which is expected to be achieved in 2019. Innovent will receive the rights to develop and commercialize the three assets in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan.

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"The collaboration and partnership with Innovent provides us with an important and strategic opportunity to further serve the oncology community around the world by potentially bringing new, innovative medicines to patients with high unmet medical needs in China," said Hervé Hoppenot, Chief Executive Officer of Incyte. "We believe Innovent’s experienced leadership team and sizeable clinical network will expand our clinical trials for itacitinib, pemigatinib and parsaclisib, and, if any of these product candidates are approved, will provide access to our innovative therapies to patients and healthcare providers in China."

"We’re very pleased to enter into this collaboration with Incyte, a well-recognized innovative global biopharmaceutical company. This collaboration not only strengthens our portfolio by adding three potentially best-in-class clinical-stage targeted therapies, but, we believe, also proves that Innovent is an ideal partner for world-class pharmaceutical companies coming to China—transforming Innovent from a company primarily focused on monoclonal antibodies to one with a broader oncology focus that develops potentially innovative treatments regardless of molecule size," said Michael DC Yu., Ph.D., Chief Executive Officer and President of Innovent. "Based on the compelling clinical data reported to-date, we believe pemigatinib, itacitinib and parsaclisib may be poised, if further development is successful and approvals in China are granted, to dramatically alter the treatment landscape for patients in China with FGFR-altered cholangiocarcinoma and urothelial carcinoma, graft-versus-host-disease after bone marrow transplant and non-Hodgkin lymphoma, respectively, and other cancers. These three novel medicines from Incyte complement our rich pipeline of immune-oncology-focused monoclonal antibodies and also enable the exploration of combination treatment approaches with the potential to further improve patient outcomes worldwide."

Per the terms of the collaboration agreement, Innovent will pay Incyte US$40 million in cash up front and Incyte will be eligible to receive an additional US$20 million in consideration in connection with the first IND filing in China, which is expected to be achieved in 2019. Innovent will receive rights to develop and commercialize three product candidates (pemigatinib, itacitinib and parsaclisib) in hematology and oncology in the Innovent territory of Mainland China, Hong Kong, Macau and Taiwan. In addition, Incyte will be eligible to receive up to US$129 million in potential development and regulatory milestones, and up to US$202.5 million in potential commercial milestones. Incyte will also be eligible to receive tiered royalties from the high teens to the low twenties on future sales of products resulting from the collaboration. Incyte retains an option to assist in the promotion of the three product candidates in China.

The transaction is effective immediately upon the execution of the strategic collaboration agreement. Further financial details were not disclosed.

About Pemigatinib (INCB54828, FGFR inhibitor)

Fibroblast growth factor receptors (FGFRs) play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating mutations, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers. Pemigatinib is an oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated potency and selective pharmacologic activity against cancer cells with FGFR alterations. Phase 2 studies investigating the safety and efficacy of pemigatinib monotherapy across several FGFR-driven malignancies are ongoing—the FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program currently comprises FIGHT-201 in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 alterations; FIGHT-202 in patients with metastatic or surgically unresectable cholangiocarcinoma who have failed previous therapy, including with activating FGFR2 translocations; and FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 translocations. FIGHT-302, a randomized Phase 3 trial in newly-diagnosed patients with cholangiocarcinoma and activating FGFR2 translocations, is expected to be initiated before the end of 2018 (NCT03656536).

About Itacitinib（INCB39110, JAK1 inhibitor）

Itacitinib (INCB039110) is a novel, potent, and selective JAK1 inhibitor currently in clinical studies for the treatment of treatment naïve acute and chronic GVHD, and non-small cell lung cancer in combination with osimertinib, an EGFR inhibitor. A Phase 3 study (GRAVITAS-301) of itacitinib for the treatment of acute GVHD is underway, with data expected in 2019. GRAVITAS-309 (NCT03584516) is a randomized, double-blind, placebo-controlled pivotal Phase 3 study evaluating itacitinib or placebo in combination with corticosteroids as a first-line treatment for patients with chronic graft-versus-host disease (cGVHD) which is expected to be initiated early in 2019.

About Parsaclisib (INCB50465, PI3Kδ inhibitor)

Parsaclisib (INCB50465) is an investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ) isoforms. PI3Kδ is an important anticancer target implicated in malignant B-cell growth, survival and proliferation which, in preclinical studies, has demonstrated potency and selectivity in preclinical studies and has potential therapeutic utility in the treatment of patients with hematologic malignancies such as lymphoma. Emerging data suggest that PI3Kδ may also be an important target in the solid tumor microenvironment. The CITADEL (Clinical Investigation of TArgeted PI3K-DELta Inhibition in Lymphomas) clinical trial program is currently evaluating parsaclisib in several ongoing Phase 2 trials as a treatment for non-Hodgkin lymphomas (follicular, marginal zone and mantle cell) Parsaclisib is also being studied in Phase 1 and Phase 2 trials as part of a combination therapy for patients with myelofibrosis, advanced or metastatic solid tumors and diffuse large B-cell lymphoma.

On December 16, 2018 Incyte (NASDAQ:INCY) and Innovent Biologics, Inc. (Innovent) (HKEX: 01801) reported that the companies, through their respective subsidiaries, have entered into a strategic collaboration agreement for three clinical-stage product candidates discovered and developed by Incyte—pemigatinib (FGFR1/2/3 inhibitor), itacitinib (JAK1 inhibitor) and parsaclisib (PI3Kδ inhibitor) (Press release, Incyte, DEC 16, 2018, View Source [SID1234532077]). Under the terms of the agreement, Innovent will pay Incyte US$40 million in cash up front, and Incyte shall be eligible to receive an additional US$20 million in consideration in connection with the first investigational new drug (IND) application by Innovent in China, which is expected to be achieved in 2019. Innovent will receive the rights to develop and commercialize the three assets in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan.

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"The collaboration and partnership with Innovent provides us with an important and strategic opportunity to further serve the oncology community around the world by potentially bringing new, innovative medicines to patients with high unmet medical needs in China," said Hervé Hoppenot, Chief Executive Officer of Incyte. "We believe Innovent’s experienced leadership team and sizeable clinical network will expand our clinical trials for itacitinib, pemigatinib and parsaclisib, and, if any of these product candidates are approved, will provide access to our innovative therapies to patients and healthcare providers in China."　

"We’re very pleased to enter into this collaboration with Incyte, a well-recognized innovative global biopharmaceutical company. This collaboration not only strengthens our portfolio by adding three potentially best-in-class clinical-stage targeted therapies, but, we believe, also proves that Innovent is an ideal partner for world-class pharmaceutical companies coming to China—transforming Innovent from a company primarily focused on monoclonal antibodies to one with a broader oncology focus that develops potentially innovative treatments regardless of molecule size," said Michael DC Yu., Ph.D., Chief Executive Officer and President of Innovent. "Based on the compelling clinical data reported to-date, we believe pemigatinib, itacitinib and parsaclisib may be poised, if further development is successful and approvals in China are granted, to dramatically alter the treatment landscape for patients in China with FGFR-altered cholangiocarcinoma and urothelial carcinoma, graft-versus-host-disease after bone marrow transplant and non-Hodgkin lymphoma, respectively, and other cancers. These three novel medicines from Incyte complement our rich pipeline of immune-oncology-focused monoclonal antibodies and also enable the exploration of combination treatment approaches with the potential to further improve patient outcomes worldwide."

Per the terms of the collaboration agreement, Innovent will pay Incyte US$40 million in cash up front and Incyte will be eligible to receive an additional US$20 million in consideration in connection with the first IND filing in China, which is expected to be achieved in 2019. Innovent will receive rights to develop and commercialize three product candidates (pemigatinib, itacitinib and parsaclisib) in hematology and oncology in the Innovent territory of Mainland China, Hong Kong, Macau and Taiwan. In addition, Incyte will be eligible to receive up to US$129 million in potential development and regulatory milestones, and up to US$202.5 million in potential commercial milestones. Incyte will also be eligible to receive tiered royalties from the high teens to the low twenties on future sales of products resulting from the collaboration. Incyte retains an option to assist in the promotion of the three product candidates in China.

The transaction is effective immediately upon the execution of the strategic collaboration agreement. Further financial details were not disclosed.

About Pemigatinib (INCB54828, FGFR inhibitor)

Fibroblast growth factor receptors (FGFRs) play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating mutations, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers. Pemigatinib is an oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated potency and selective pharmacologic activity against cancer cells with FGFR alterations. Phase 2 studies investigating the safety and efficacy of pemigatinib monotherapy across several FGFR-driven malignancies are ongoing—the FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program currently comprises FIGHT-201 in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 alterations; FIGHT-202 in patients with metastatic or surgically unresectable cholangiocarcinoma who have failed previous therapy, including with activating FGFR2 translocations; and FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 translocations. FIGHT-302, a randomized Phase 3 trial in newly-diagnosed patients with cholangiocarcinoma and activating FGFR2 translocations, is expected to be initiated before the end of 2018 (NCT03656536).

About Itacitinib（INCB39110, JAK1 inhibitor）

Itacitinib (INCB039110) is a novel, potent, and selective JAK1 inhibitor currently in clinical studies for the treatment of treatment naïve acute and chronic GVHD, and non-small cell lung cancer in combination with osimertinib, an EGFR inhibitor. A Phase 3 study (GRAVITAS-301) of itacitinib for the treatment of acute GVHD is underway, with data expected in 2019. GRAVITAS-309 (NCT03584516) is a randomized, double-blind, placebo-controlled pivotal Phase 3 study evaluating itacitinib or placebo in combination with corticosteroids as a first-line treatment for patients with chronic graft-versus-host disease (cGVHD) which is expected to be initiated early in 2019.

About Parsaclisib (INCB50465, PI3Kδ inhibitor)

Parsaclisib (INCB50465) is an investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ) isoforms. PI3Kδ is an important anticancer target implicated in malignant B-cell growth, survival and proliferation which, in preclinical studies, has demonstrated potency and selectivity in preclinical studies and has potential therapeutic utility in the treatment of patients with hematologic malignancies such as lymphoma. Emerging data suggest that PI3Kδ may also be an important target in the solid tumor microenvironment. The CITADEL (Clinical Investigation of TArgeted PI3K-DELta Inhibition in Lymphomas) clinical trial program is currently evaluating parsaclisib in several ongoing Phase 2 trials as a treatment for non-Hodgkin lymphomas (follicular, marginal zone and mantle cell) Parsaclisib is also being studied in Phase 1 and Phase 2 trials as part of a combination therapy for patients with myelofibrosis, advanced or metastatic solid tumors and diffuse large B-cell lymphoma.

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.

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"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.

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]).

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"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.

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.