On October 25, 2019 NuCana plc (NASDAQ: NCNA) reported that the US Food and Drug Administration (FDA) has cleared the Investigational New Drug Application (IND) for its Phase III study (NuTide:121) of the investigational drug Acelarin in combination with cisplatin for patients with previously untreated locally advanced or metastatic biliary tract cancer (Press release, Nucana BioPharmaceuticals, OCT 25, 2019, View Source [SID1234542521]).

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"We are pleased to have received clearance of our IND from the FDA," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "We are also excited by NuTide:121’s potential, if successful, to support both accelerated and full approval. Regulatory clearance to begin the study in other countries has also been received and we look forward to enrolling the first patients in the coming weeks."

Mr. Griffith continued: "We believe our investigational drug product Acelarin in combination with cisplatin has the potential to significantly improve the survival outcomes of patients with advanced biliary tract cancer. In the Phase Ib ABC-08 study, we observed an approximate doubling of the response rate with Acelarin plus cisplatin compared to previously reported data for gemcitabine plus cisplatin. Our goal is to establish Acelarin in combination with cisplatin as the global standard of care for the first-line treatment of patients with advanced biliary tract cancer, if Acelarin is approved for marketing."

NuTide:121 will be a global, multi-center, randomized Phase III study that will enroll up to 828 patients in approximately 120 sites across North America, Europe, Asia and Australia. Patients will be randomized 1:1 and treated with either a combination of Acelarin (725 mg/m2) plus cisplatin (25 mg/m2) or the current standard of care regimen, gemcitabine (1,000 mg/m2) plus cisplatin (25 mg/m2).

The primary objectives of NuTide:121 are Overall Survival (OS) and Objective Response Rate (ORR). Three interim analyses, including two designed to support accelerated approval, are planned as part of the Phase III study protocol in addition to the final analysis. Based on discussions with the FDA and subject to any further regulatory guidance, the Company believes that a statistically significant improvement in ORR at either of the first two interim analyses, supported by positive trends in other endpoints, could potentially allow for an accelerated approval of a new drug application (NDA) for Acelarin. Accelerated approval requires a confirmatory clinical study to verify the drug’s clinical benefit. If accelerated approval were to occur, NuTide:121 would continue and the Company anticipates that data from subsequent analyses could provide the confirmatory data to support full (regular) approval.

Dr. Jennifer J. Knox, Professor of Medicine at the University of Toronto, Clinician Investigator at the Princess Margaret Cancer Centre and Chief Investigator of NuTide:121 stated: "I am very excited to be leading the NuTide:121 study. I believe Acelarin plus cisplatin may represent an important advance in the treatment of biliary tract cancer, a devastating disease for which there is a significant need for more effective medicines."

Dr. Juan Valle, Professor and Honorary Consultant in Medical Oncology at the University of Manchester and The Christie, Manchester, United Kingdom was Chief Investigator of the ABC-02 study that established gemcitabine plus cisplatin as the current standard of care for the first-line treatment of patients with advanced biliary tract cancer. Professor Valle said: "As Co-Chief Investigator of the ABC-08 Phase Ib Study, I was encouraged by the efficacy signals observed with Acelarin plus cisplatin, so I am enthusiastic about further investigating Acelarin in combination with cisplatin in NuTide:121, the largest study ever conducted in patients with advanced biliary tract cancer."

NuTide:121 Statistical Analysis Plan (SAP)

Three interim efficacy analyses, including two designed to support accelerated approval of Acelarin in the United States, are currently planned in addition to the final analysis.

The first interim analysis will evaluate the ORR primary endpoint and will be performed 22 weeks after 418 patients with measurable disease at baseline have been randomized. A statistically significant difference in ORR at this analysis would require the Acelarin plus cisplatin arm to have an ORR at least 14% higher than that of the gemcitabine plus cisplatin arm.

The second interim analysis will evaluate the ORR and OS primary endpoints. It will be performed 28 weeks after 644 patients with measurable disease at baseline have been randomized. A statistically significant difference in ORR at this analysis would require the Acelarin plus cisplatin arm to have an ORR approximately 9% higher than that of the gemcitabine plus cisplatin arm. If a statistically significant difference in ORR is detected, OS will also be analyzed at this analysis and a difference in median OS of approximately 3.4 months in favor of Acelarin plus cisplatin would be deemed a statistically significant improvement in OS.

The third interim analysis will evaluate the OS primary endpoint and will take place after 541 events have been observed. A statistically significant difference for OS in favor of Acelarin plus cisplatin would be achieved with an improvement in median OS of approximately 2.6 months.

The final analysis will evaluate the OS primary endpoint. It will take place after 637 events have been observed. A statistically significant difference for OS in favor of Acelarin plus cisplatin would be achieved with an improvement in median OS of approximately 2.2 months.

On October 25, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis) for the treatment of various cancers including prostate, colorectal and leukemia, reported that it has entered into definitive agreements with institutional investors for the sale of 2,756,340 shares of common stock (or common stock equivalents), series G warrants to purchase up to 2,756,340 shares of common stock, and series H warrants to purchase up to 2,756,340 shares of common stock in a private placement at a price of $1.814 per share and associated warrants for gross proceeds of approximately $5.0 million (Press release, Trovagene, OCT 25, 2019, View Source [SID1234542539]). The transaction is anticipated to close on or about October 29, 2019, subject to customary closing conditions.

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H.C. Wainwright & Co. is acting as exclusive placement agent for the offering.

The series G warrants are exercisable immediately with a term of five and one-half years and an exercise price of $1.56 per share. The series H warrants are exercisable immediately with a term of 18 months and an exercise price of $1.56 per share.

Trovagene intends to use the net proceeds of the private placement to fund clinical development activities and for working capital and general corporate purposes. The Company has agreed to file a resale registration statement for the shares of common stock and the shares of common stock underlying the warrants issued in the offering within 10 days pursuant to a registration rights agreement.

The securities sold in the private placement have not been registered under the Securities Act of 1933, as amended, or state securities laws and may not be offered or sold in the United States absent registration with the Securities and Exchange Commission (SEC) or an applicable exemption from such registration requirements.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

Further information regarding the private placement can be found in the Current Report on Form 8-K that will be filed by the Company with the SEC.

On October 25, 2019 Helix BioPharma Corp. (TSX: "HBP"), an immuno-oncology company developing drug candidates for the prevention and treatment of cancer, reported its financial results for the year ended July 31, 2019 (Press release, Helix BioPharma, OCT 25, 2019, View Source [SID1234542524]).

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FINANCIAL REVIEW

The Company recorded a net loss and total comprehensive loss of $7,526,000 and $8,625,000 (a loss per common share of $0.07 and $0.09) for the fiscal years ended July 31, 2019 and 2018 respectively.

Research and development

Research and development expenses totalled $6,084,000 and $6,524,000, respectively for the twelve-month periods ended July 31, 2018 and 2017.

The following table outlines research and development costs expensed and investment tax credits for the Company’s significant research and development projects for the fiscal years ended July 31:

L-DOS47 research and development expenses for fiscal 2019 totalled $3,530,000 (2018 – $4,893,000). L-DOS47 research and development expenditures relate primarily to the Company’s LDOS001 Phase I clinical study in the U.S., the LDOS002 European Phase I/II clinical study in Poland, the LDOS003 Phase II clinical study in Poland and the Ukraine and the Company’s newly approved Phase Ib/II clinical study in the U.S.

The Company’s overall reduction in research and development spend when compared to the previous fiscal year is the result of the Company’s non-small cell lung cancer studies (LDOS001, and LDOS002) all being in the late stage of development within their respective clinical phases while at the same time, the Company started ramping up activity of its newly approved investigational new drug clinical study for advanced pancreatic cancer (LDOS006).
Patient recruitment for LDOS001 was closed on July 1, 2019. The Company expects to have a final clinical study report for LDOS001 no later than the first calendar quarter of 2020. As for LDOS002, all analyses have been completed and a draft clinical study report is currently under review and expected to be finalized by the end of calendar 2019. LDOS003 is currently in the last cohort awaiting one more patient to be enrolled to complete the dose escalating portion of the study. The Company has indicated that it would not be moving forward into the randomized portion of the study unless certain clinical objectives are met in the dose escalating phase and sufficient capital is obtained, or the Company enters into a co-development partnership with a third party. The Company expects to start enrolling patients in LDOS006 starting December 2019.

The Company’s Polish subsidiary entered into a grant funding agreement with the National Centre for Research and Development for research and development expenditures associated with V-DOS47. V-DOS47 research and development expenses for fiscal 2019 totalled $478,000 (2018 – $457,000). Research and development expenditures in the program remained flat when compared to fiscal 2018. In fiscal 2019, the Company’s Polish subsidiary received grant funding of $479,000 (2018 – $475,000). The Company previously disclosed that it was looking to dispose of its ownership position in its Polish subsidiary while retaining licensing agreement for future milestones and royalty payments. More recently, as part of a financing on August 21, 2019 for gross proceeds of $7,000,005, the Company disposed 25% of its investment in its Polish subsidiary. The Company’s plans to divest its entire interest in its Polish subsidiary while retaining agreements for future milestone and royalties.

CAR-T research and development expenses for fiscal 2019 totalled $333,000 (2018 – $318,000). The Company commenced development of novel CAR-T therapeutics and new antibody-based technologies for cell-based therapies. The Company’s CAR-T expenditures relate primarily to collaborative research activities with ProMab Biotechnologies Inc.

Corporate research and development expenses for fiscal 2019 totalled $528,000 (2018 – $432,000). The increase in corporate research and development expenditures mainly represents a bonus payout to the Chief Executive Officer.

Trademark and patent related expenses for fiscal 2019 totalled $435,000 (2018 – $440,000). The Company continues to ensure it adequately protects its intellectual property.

Operating, general and administration

Operating, general and administration expenses for fiscal 2019 totalled $2,486,000 (2018 – $2,462,000). Operating, general and administration expenses remained relatively flat. The Increase in wages and benefits and stock-based compensation were offset by a reduction in lower director fees and other general and administrative expenditures. The increase in wages & benefits and stock-based compensation is the result of a bonus payout to the CFO and stock options granted to administrative employees and non-management directors. The reduction in director fees reflects a reduction in committee and board meetings held as well as a reduction in the number of directors on the board of the company. Limited working capital throughout the year resulted in reductions in other general and administrative spending activity.

LIQUIDITY AND CAPITAL RESOURCES

As at July 31, 2019 the Company had a working capital deficiency of $3,534,000 (2018 – $1,901,000), shareholders’ deficiency of $3,281,000 (2018 – $1,527,000) and a deficit of $171,531,000 (2018 – $164,005,000).

The Company raised gross proceeds of approximately $6,523,000 in fiscal 2019. The Company’s cash reserves of $206,000 as at July 31, 2019 in addition to the subsequent private placements the Company closed on August 21, 2019 for gross proceeds of approximately $7,000,005 are insufficient to meet anticipated cash needs for working capital and capital expenditures through the next twelve months, and nor are they sufficient to see planned research and development initiatives through to completion. Though the funds raised have assisted the Company in dealing with its working capital deficiency, additional funds are required to advance the Company’s clinical and preclinical programs and deal with working capital requirements 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’s Consolidated Statement of Net Loss and Comprehensive Loss and Consolidated Statement of Cash Flow for fiscal 2019 and 2018 are summarized below:

The Company’s consolidated financial statements, management’s discussion and analysis and annual information form will be filed under the Company’s profile on SEDAR at www.sedar.com, as well as on the Company’s website at www.helixbiopharma.com.

On October 25, 2019 Y-mAbs Therapeutics, Inc. (the Company or Y-mAbs) (Nasdaq: YMAB) a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that a clinical update on one of the Company’s lead products, naxitamab for the treatment of neuroblastoma and osteosarcoma, was made at the International Society of Pediatric Oncology (SIOP) Annual Congress held in Lyon, France (Press release, Y-mAbs Therapeutics, OCT 25, 2019, View Source [SID1234542525]). Naxitamab is currently being evaluated for the treatment of pediatric patients with relapsed or refractory high-risk neuroblastoma, osteosarcoma and other GD2-positive tumors. An oral presentation was made by Dr. Shakeel Modak, and a total of five (5) poster presentations were made by Dr. Brian H. Kushner and Dr. Filemon Dela Cruz, all from Memorial Sloan Kettering (MSK) in New York.

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Data from 28 patients with primary refractory high-risk neuroblastoma in Study 12-230 (NCT01757626) was presented. This comprises patients refractory to intensive induction therapy, and more than half of such patients also refractory to second line chemotherapy. Essentially, this data relates to a subset of patients from Study 12-230 that demonstrate better than expected outcomes, including a 78% overall response rate. The patients received at least five (5) cycles of therapy post major response and a subset subsequently went on to receive the Company’s investigational GD2-GD3 Vaccine at MSK. Overall, in this population a 50% two-year progression free survival was observed.

Another subset consisted of 35 patients with relapsed neuroblastoma resistant to salvage therapy, of which 30 patients were evaluable for response in the 12-230 Study. One third of the patients had two (2) or more relapses prior to enrollment and 89% of patients had previously received anti-GD2 therapy. Patients in this subset had a 36% rate of two-year progression-free survival and an overall response rate (ORR) of 37%, which indicated clinical benefit in this difficult to treat population.

Data was also presented for patients with high-risk neuroblastoma in second or later complete remission. 44 patients with no evidence of disease (NED) were treated with naxitamab and GM-CSF at MSK as maintenance therapy. In this population, where 88% had previously received an anti-GD2 therapy and 30% had previously received two or more lines of anti-GD2 therapy, a two-year progression-free survival of 52% was observed. Some of these patients went on to receive the Company’s investigational GD2-GD3 Vaccine at MSK. Due to the absence of macroscopic evaluable disease, these patients were not evaluable for a formal tumor response grading. Therefore, these patients will not form a part of the Company’s efficacy data set for its rolling biologics license application (BLA) filing currently planned to be initiated in November 2019.

Finally, safety data from the Phase II osteosarcoma trial, Study 15-096, for the 25 patients enrolled in the study at MSK was presented. Patients who had recurrent disease and two (2) or more complete remissions were treated with naxitamab and GM-CSF, administered to the patients in an outpatient setting. The Company plans to initiate a multi-center trial in 2020.

"It is both exciting and encouraging to see the efficacy data that naxitamab produces in neuroblastoma and the safety data in osteosarcoma presented this week at SIOP. We believe that we are on track to initiate the rolling BLA filling for naxitamab in combination with GM-CSF for the treatment of relapsed/refractory high-risk neuroblastoma in November this year under the breakthrough therapy designation (BTD), which the Company previously received from the FDA," said Thomas Gad, Founder, Chairman, President and Head of Business Development and Strategy.

Dr. Claus Moller, Chief Executive Officer, further noted, "We are very pleased to see the response rates previously reported from Study 12-230 holding up. We are genuinely impressed with the duration of responses, and we have also observed this being replicated for the 24 patients in our international multicenter Study 201, which, we believe, will be pivotal for our rolling BLA filing for naxitamab. Based on our pre-BLA meeting with the FDA in June 2019, where data from the first 11 patients from Study 201 had been analyzed and showed a more than 70% overall response rate, we believe the response rate seems to be holding up for the complete group of patients in Study 201. We believe that this is good news for neuroblastoma patients."

On October 25, 2019 SRI researchers reported it will present data from multiple programs exploring novel approaches to cancer drug targeting and delivery (Press release, SRI International, OCT 25, 2019, View Source [SID1234548674]). This includes a novel technology that leverages the immune system in a new way – by tricking it into thinking cancer cells are infected with a serious virus.

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Abstract C018. Primary tumor data analysis reveals novel synthetic lethal dependencies between KRAS mutation and the spliceosome
Date/Time: Tuesday, October 29, 12:30 p.m. ET
Hall D, Hynes Convention Center

Abstract 467. Cancer-Specific Intracellular Delivery of Therapeutic Antibodies Against RAS
Date/Time: Tuesday, October 29, 12:30 p.m. ET
Hall D, Hynes Convention Center

Abstract 463. A Novel Cell-Mediated Immunotherapy for Treatment of Lung and Breast Cancer
Date/Time: Monday, October 28, 12:30 p.m. ET
Hall D, Hynes Convention Center