On October 25, 2019 Ventas, Inc. (NYSE: VTR) reported its results for the third quarter ended September 30, 2019 (Press release, Ventas, OCT 25, 2019, View Source [SID1234542531]).

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!

"Ventas delivered strong enterprise level results in the third quarter, driven by our diverse portfolio including robust performance in our Medical Office, Healthcare and Research & Innovation portfolios, our high quality and accretive investments and effective capital markets execution. We have maintained the midpoint of our normalized FFO per share expectations for 2019, and we continue to invest in our future," said Debra A. Cafaro, Ventas Chairman and CEO.

Cafaro added, "Given challenging senior housing market conditions, our senior housing operating portfolio did not perform consistent with historical patterns or our expectations in the quarter, a trend we expect to continue for the balance of the year. As a result, while national leading indicators of supply and demand in the senior housing sector continue to improve, giving us confidence in the powerful upside that lies ahead, we have reduced our 2019 property level guidance for our senior housing operating business. This changed expectation leads us to conclude that our return to enterprise growth will occur after 2020.

"We have built a strong, diverse and resilient business well positioned to capitalize on strong demographic demand growth. We are committed to enhancing value for shareholders and are taking actions that will improve performance and deliver growth and value."

Third Quarter 2019 Company Performance

Net income attributable to common stockholders per diluted share for the third quarter 2019 was $0.23 compared to $0.28 in the same period in 2018. The year-over-year change was principally driven by the positive contribution from new investments, more than offset by higher depreciation and amortization in the third quarter 2019 and the receipt of a $12 million cash fee (the "2018 Fee") in the third quarter of 2018.
Reported Funds from Operations per share, as defined by the National Association of Real Estate Investment Trusts ("Nareit FFO") was $0.84 compared to $0.88 in the same period in 2018. The change from 2018 results was due to the factors described above, excluding the impact of depreciation and amortization.
Normalized Funds from Operations ("FFO") per share for the third quarter 2019 was $0.96 compared to $0.99 in 2018. The change from 2018 was primarily the result of growth in income from new investments, more than offset by the receipt of the 2018 Fee in the third quarter of 2018.
Third Quarter 2019 Portfolio Performance

For the third quarter 2019, the Company’s quarterly same-store total property portfolio (1,107 assets, representing 93 percent of the company’s consolidated assets) cash net operating income ("NOI") rose 0.1 percent compared to the same period in 2018. Year-to-date 2019, the Company’s full year same-store total property portfolio (1,094 assets) cash NOI grew 0.5 percent compared to the same period in 2018. Reported same-store cash NOI performance by segment for the third quarter 2019 and year-to-date 2019 are as follows:

Third quarter year-over-year changes in the Company’s same-store property results were driven by:
NNN portfolio: Growth was primarily the result of net in-place lease escalations.
SHOP portfolio: Same-store SHOP performance was below expectations, driven by the cumulative effect of new openings in a dynamic competitive market, which pressured revenue. While average third quarter 2019 occupancy was 70 basis points lower than the third quarter 2018, the year-over-year occupancy gap widened materially in September, ending the quarter approximately 115 basis points lower than third quarter-end 2018. Meanwhile, price competition drove wider re-leasing spreads year-over-year. Industry-wide, senior housing demand is accelerating and the positive trend of lower new construction starts continued, particularly in assisted living, where fewer than 1,000 units broke ground in the quarter in primary markets.
Office portfolio: Growth was led by outstanding performance in the Company’s university-based Research & Innovation ("R&I") properties and complemented by steady growth in the Company’s medical office building ("MOB") portfolio, which is benefitting from the implementation and success of operational and sustainability initiatives. Third quarter 2019 office results included a $4.7 million cash lease termination fee, which was not included in same-store results.
2019 Investment Highlights

The Company has announced $3.8 billion in year-to-date investments (at 100 percent share), including $1.8 billion in Le Groupe Maurice and $900 million in attractive R&I developments. Investment highlights from the quarter include:

Completed Portfolio Investment with Le Groupe Maurice ("LGM"): As previously announced, Ventas completed its investment in a Class A portfolio of 29 operating apartment-like senior housing assets in the attractive Quebec market, and five in-progress developments, through an equity partnership with LGM (the "LGM Acquisition"). The LGM portfolio is fully integrated and performing well.
Investment in Future Growth in R&I Development: Ventas accelerated its investments in future growth through new developments in the third quarter 2019, driven principally by the R&I development pipeline. Recent updates include:
Pitt Immune Transplant & Therapy Center:Commenced construction on a $280 million, 350,000 square foot development that is 70 percent pre-leased to the University of Pittsburgh with strong incremental leasing demand.
College of Nursing and Health Professions, Drexel University: Executed a 30-year lease with Drexel University for a new development that will house Drexel’s College of Nursing and Health Professions in the uCity Square Knowledge Community ("uCity"). Drexel’s lease is for 100 percent of the building, which will be approximately 260,000 square feet and produce an expected GAAP yield of nearly 10 percent. Construction of the College of Nursing and Health Professions is expected to commence by mid-2020 and the building is set to open by 2022.
Expanding uCity: The Ventas uCity in-place portfolio is currently 98 percent leased with robust demand, including for the recently announced One uCity development. In the third quarter of 2019, Ventas acquired land and other assets in the thriving Philadelphia uCity market, supporting an additional 450,000 square feet of developable space.
Expanding Ardent Investment at Attractive Yield: Ventas began funding a $28 million investment in the development of a new on-campus outpatient cancer center, Harrington Cancer Center, leased to Ardent Health System at an approximately eight percent cash yield, which is expected to be completed in 2021.
Redevelopment: Ventas committed to invest $36 million in redevelopment capital projects in the third quarter 2019 across four medical office buildings leased to Banner Health in Phoenix, Arizona, as well as $15 million across several SHOP assets focused on LED lighting retrofits with various operators.
2019 Office Excellence

Ventas’s office business delivered exceptional performance and achievements year to date:

The R&I portfolio delivered outstanding third quarter 2019 growth, including occupancy levels approaching 97 percent and year-over-year cash same-store NOI growth exceeding 10 percent supported by continued leasing success.
The MOB portfolio, composed of 20 million square feet, demonstrated strong positive trends on tenant satisfaction and retention, resulting from the Company’s focused efforts.
Ventas’s South Street Landing near Brown University won a Richard H. Driehaus Foundation National Preservation Award for its historic preservation work.
Financial Strength and Liquidity

Ventas’s Net Debt to Adjusted Pro Forma EBITDA ratio was 5.9x in the third quarter. As anticipated, leverage increased sequentially principally as a result of the timing of equity raised in the second quarter and the completion of the LGM Acquisition in the third quarter.
Third quarter and recent capital market activity includes:
The Company extended its maturity profile and managed interest rate risk via the issuance of $650 million of 3.00% Senior Notes due 2030, the proceeds of which were used to retire $600 million of 4.25% Senior Notes due 2022.
Ventas managed currency risk by financing a portion of the LGM Acquisition in Canadian dollars through the closing of a C$500M unsecured bank term loan in September. The term loan is attractively priced at CDOR + 90 basis points and matures in January 2025.
The Company had robust available liquidity from cash on hand and existing credit facilities totaling $1.8 billion at the end of the third quarter 2019, net of outstanding commercial paper.
Demonstrated Leadership Excellence and Commitment to ESG (Environmental, Social, Governance) Principles

Ms. Cafaro was again recognized as one of Harvard Business Review’s Top 100 Best Performing CEOs in the World for the sixth consecutive year. She is one of only 14 global CEOs who have been named to HBR’s list consistently since 2014, placing Ventas’s financial accomplishments in the top four percent of all firms measured. In addition, the Company’s non-financial performance metrics significantly improved in 2019 to its highest ever rating for the two ESG measures which make up 30% of the result.
Ventas was named to the Dow Jones Sustainability World Index for the first time and retained its place on the Dow Jones Sustainability North America Index ("DJSI"). The first global sustainability benchmark to track the largest and leading sustainability-driven publicly listed companies, only companies that rank within the top 10 percent of their industries are included in the DJSI World Index.
Ventas maintained its #1 position among the four listed healthcare real estate participants in the GRESB real estate ESG assessment for the third consecutive year. GRESB is a premier ESG benchmark for real assets, and covers more than 1,000 property companies, REITs, funds and developers.
Ventas released its second annual Corporate Sustainability Report ("CSR") earlier today. Ventas’s 2019 CSR describes the Company’s achievements, and reaffirms its commitment to ESG leadership. The CSR, which was produced consistent with globally recognized best practices, also details Ventas’s enhanced strategic ESG framework and newly-established ESG goals.
Third Quarter Dividend

The Company paid its third quarter 2019 dividend of $0.7925 per share on October 11, 2019 to stockholders of record on October 1, 2019.

Updated 2019 Guidance

Ventas is updating its outlook for 2019 per share net income attributable to common stockholders, Nareit FFO and normalized FFO, as described below. The Company is also updating its previous overall and segment same-store cash NOI growth guidance.

Assumptions for Ventas’s 2019 updated normalized FFO per share guidance are materially consistent with the Company’s previously disclosed guidance, and include the impacts of announced investments and associated capital markets activities. Total same-store guidance has been updated to reflect revisions to segment-level outlooks, with office and NNN increases more than offset by a reduction in SHOP expectations. The SHOP guidance change reflects third quarter revenue trends, a dynamic and competitive market, and lower occupancy levels entering the fourth quarter. With respect to the Company’s NNN senior housing portfolio, the Company continues to estimate that it will incur approximately a ($10 million) net impact to its NOI from proactively addressing leases with select lower credit operators, which impact is contained in non-same store results.

A reconciliation of the Company’s 2019 guidance to the Company’s projected GAAP measures is included in this press release. The Company’s 2019 guidance is based on a number of other assumptions that are subject to change and many of which are outside the control of the Company. If actual results vary from these assumptions, the Company’s expectations may change. There can be no assurance that the Company will achieve these results.

Third Quarter 2019 Conference Call

Ventas will hold a conference call to discuss this earnings release today at 10:00 a.m. Eastern Time (9:00 a.m. Central Time). The dial-in number for the conference call is (844) 776-7841 (or +1 (661) 378-9542 for international callers), and the participant passcode is "Ventas." The call will also be webcast live by NASDAQ OMX and can be accessed at the Company’s website at www.ventasreit.com. A replay of the call will be available at the Company’s website, or by calling (855) 859-2056 (or +1 (404) 537-3406 for international callers), passcode 4816549, beginning on October 25, 2019, at approximately 1:00 p.m. Eastern Time and will remain available for 30 days.

Ventas, Inc., an S&P 500 company, is a leading real estate investment trust. Its diverse portfolio of approximately 1,200 assets in the United States, Canada and the United Kingdom consists of senior housing communities, medical office buildings, university-based research and innovation centers, inpatient rehabilitation and long-term acute care facilities, and health systems. Through its Lillibridge subsidiary, Ventas provides management, leasing, marketing, facility development and advisory services to highly rated hospitals and health systems throughout the United States. References to "Ventas" or the "Company" mean Ventas, Inc. and its consolidated subsidiaries unless otherwise expressly noted. More information about Ventas and Lillibridge can be found at www.ventasreit.com and www.lillibridge.com.

The Company routinely announces material information to investors and the marketplace using press releases, Securities and Exchange Commission ("SEC") filings, public conference calls, webcasts and the Company’s website at www.ventasreit.com/investor-relations. The information that the Company posts to its website may be deemed to be material. Accordingly, the Company encourages investors and others interested in the Company to routinely monitor and review the information that the Company posts on its website, in addition to following the Company’s press releases, SEC filings and public conference calls and webcasts. Supplemental information regarding the Company can be found on the Company’s website under the "Investor Relations" section or at www.ventasreit.com/investor-relations/annual-reports—supplemental-information. A comprehensive listing of the Company’s properties is available at www.ventasreit.com/our-portfolio/properties-by-stateprovince.

On October 25, 2019 Pacira BioSciences, Inc. (NASDAQ:PCRX) reported that it will report its third quarter financial results before the open of the U.S. markets on Thursday, November 7, 2019 (Press release, Pacira Pharmaceuticals, OCT 25, 2019, View Source [SID1234542530]). Following the release, the company will host a live conference call and webcast at 8:30 a.m. ET.

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!

To participate in the conference call, dial 1-877-845-0779 and provide the passcode 8077145. International callers may dial 1-720-545-0035 and use the same passcode. In addition, a live audio of the conference call will be available as a webcast. Interested parties can access the event through the "Events" page on the Pacira website at investor.pacira.com.

For those unable to participate in the live call, a replay will be available at 1-855-859-2056 (domestic) or 1-404-537-3406 (international) using the passcode 8077145. The replay of the call will be available for one week from the date of the live call. The webcast will be available on the Pacira website for approximately two weeks following the call.

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.

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!

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 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]).

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!

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 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]).

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!

"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.