On November 12, 2019 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage immunotherapy company developing the next generation of novel T cell therapies for patients suffering from cancer, reported financial results for the third quarter ended September 30, 2019 and provided a corporate update (Press release, TCR2 Therapeutics, NOV 12, 2019, View Source [SID1234551113]).

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 continued to make clinical progress in the third quarter of 2019 and are positioned to deliver data for our two lead programs next year with interim updates anticipated from the ongoing Phase 1 portion of the TC-210 trial and the upcoming Phase 1 portion of the TC-110 trial," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "2020 represents an important period for the Company in establishing TRuC-T Cells as a viable therapeutic option for cancer patients. We look forward to providing updates not only on TC-210 and TC-110 but also on additional targets and enhancements designed to combat the harsh tumor microenvironment."

Recent Developments

TCR2 expanded the executive team with the appointment of Angela Justice, Ph.D., as its first Chief People Officer. In her new role, Dr. Justice will be responsible for leading all aspects of TCR2’s human resources function including further development of the Company’s commitment to a performance-driven culture of innovation and Human Capital strategy.

Anticipated Milestones

TCR2 anticipates an interim update of the Phase 1 portion of the TC-210 Phase 1/2 clinical trial for patients with mesothelin-expressing solid tumors in 1H20.

TCR2 anticipates an interim update of the upcoming Phase 1 portion of the TC-110 Phase 1/2 clinical trial for patients with CD19+ non-Hodgkin lymphoma or adult acute lymphoblastic leukemia in 2H20.

TCR2 remains on track to be operational at its manufacturing facility in Stevenage, UK, by year end.

Financial Highlights

Cash Position: TCR2 ended the third quarter of 2019 with $169.0 million in cash, cash equivalents, and investments compared to $123.2 million as of December 31, 2018. Net cash used in operations was $31.0 million in the first nine months of 2019 compared to $12.3 million in the first nine months of 2018. TCR2 projects net cash use of $45-50 million in 2019.

R&D Expenses: Research and development expenses were $11.4 million for the third quarter of 2019 compared to $5.4 million for the third quarter of 2018. The increase in R&D expenses is primarily related to increase in headcount, activities related to the Phase 1/2 clinical trial of the Company’s lead solid tumor product candidate, TC-210, and activities related to the IND submission of the Company’s lead hematologic cancer product candidate, TC-110.

G&A Expenses: General and administrative expenses were $3.5 million for the third quarter of 2019 compared to $1.7 million for the third quarter of 2018. The increase in general and administrative expenses was primarily due to an increase in personnel costs and costs associated with operations as a public company.

Net loss: Net loss was $13.8 million for the third quarter of 2019 compared to $6.4 million for the third quarter of 2018, driven predominantly by increased R&D expense in the quarter.

Upcoming Events

TCR2 Therapeutics management are scheduled to participate at the following upcoming conferences.

Jefferies 2019 London Healthcare Conference: Garry E. Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics, will present on Wednesday, November 20, 2019 at 11:20AM GMT in London, UK.

The 31st Annual Piper Jaffray Healthcare Conference: M. Ian Somaiya, Chief Financial Officer of TCR2 Therapeutics, will present on Wednesday, December 4, 2019 at 9:30AM ET in New York, NY.

On November 12, 2019 Oncolytics Biotech Inc. (NASDAQ:ONCY) (TSX:ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported its financial results and operational highlights for the quarter ended September 30, 2019 (Press release, Oncolytics Biotech, NOV 12, 2019, View Source [SID1234551161]). All dollar amounts are expressed in Canadian currency unless otherwise noted.

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 finished the third quarter with a little over twelve million dollars on the balance sheet and have since added to that balance with warrants exercised since the quarter’s end" said Dr. Matt Coffey, President and CEO of Oncolytics Biotech. "The quarter was marked by continued clinical execution and additional clinical validation of our systemically delivered oncolytic virus, as we continued to advance two key clinical studies that will determine the design of the phase three program for pelareorep in metastatic breast cancer. First is the AWARE-1 study, which is enrolling patients and will report additional data before year end, and second is the BRACELET-1 study, which we are co-developing with Pfizer and Merck KGaA, and will begin enrolling in Q1 2020. Both studies are designed to evaluate pelareorep in combination with leading checkpoint inhibitors and confirm the clinical utility of our novel biomarker measuring T cell clonality to predict patient response to the combination regimen."

"In parallel, pelareorep continues to gain validation and recognition among the medical community," said Dr. Rita Laeufle, Chief Medical Officer at Oncolytics. "We announced that a meta-analysis of thirteen clinical studies of pelareorep was presented, providing definitive proof that our virus can selectively infiltrate, replicate within, and inflame a diverse range of solid and hematological tumors, including metastatic disease, following systemic delivery. This is a key differentiator for pelareorep and speaks to the breadth of commercial opportunities that may be available to Oncolytics beyond our lead indication of breast cancer. Other opportunities include additional synergies, such as the recent data from preclinical combinations with CDK 4/6 inhibitors that was presented at the International Oncolytics Virus Conference in October. The preliminary data suggests that pelareorep synergizes with CDK4/6 inhibitors by blocking cellular signaling pathways triggering a process called immunogenic cell death, resulting in another very effective way to make a cold tumor very hot. These are early results, but this drug class is important enough that these advancements can definitely play a role in our business development activities."

Select highlights since July 1, 2019

Clinical & Scientific Updates

Announced preliminary AWARE-1 data demonstrating viral replication and promotion of inflammation following systemic administration of pelareorep when combined with Tecentriq.
Presented AWARE-1 data at the Society of Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) conference highlighting the replication of pelareorep exclusively in tumor tissue and an increase in inflammatory cells through the expansion of existing T cell clones, as well as the creation of new T cell clones. Data also demonstrated that pelareorep changes the immunogenetic environment within the tumor, and the results of this early stage breast cancer study support the use of T cell clonality as a biomarker and its potential value in predicting tumor response in BRACELET-1.
Presented the results of a meta-analysis of 13 clinical studies of pelareorep during a podium presentation at the annual International Oncolytic Virus Conference (IOVC). The analyses examined the effectiveness of viral replication within the tumors of patients treated systemically with pelareorep and demonstrated that, unlike other oncolytic viruses that require intra-tumoral delivery, intravenous systemic delivery of pelareorep resulted in 81% of patient tumor samples across multiple types of cancer testing positive for virus replication, with no infection in normal tissue. These results are from studies across a broad range of solid and liquid tumors, including metastatic disease, and the average increases to 96% when melanoma skin biopsies are excluded.
Provided an update on Adlai Nortye’s clinical progress and approval by the National Medical Products Administration (NMPA) of China for initiating a phase 3 clinical trial for pelareorep. The proposed study, initially based on positive results from the randomized phase 2 metastatic breast cancer study IND-213, will be finalized based on data from Oncolytics’ AWARE-1 breast cancer study in combination with Roche’s Tecentriq and BRACELET-1 metastatic breast cancer study in combination with Pfizer’s and Merck KGaA’s Bavencio.
Announced the publication of positive results from its previously announced phase 1b REO 024 study of pelareorep in combination with Merck’s Keytruda in the peer-reviewed medical journal Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). Academic collaborators presented preclinical data at IOVC on the synergies between pelareorep and CDK 4/6 inhibitors, suggesting pelareorep synergizes with CDK4/6 inhibitors by blocking cellular signaling pathways and releasing more double-stranded RNA into the tumor cell, triggering immunogenic cell death, resulting in another effective way to make a cold tumor very hot.
Corporate Updates

Announced the appointment of Leonard Kruimer, MBA, CPA, to Oncolytics’ Board of Directors.
Announced that President and Chief Executive Officer, Matt Coffey, Ph.D., MBA, was presented with the Scientific Achievement and Innovation Award by BioAlberta, the province’s life sciences industry association.
Closed an underwritten public share offering of USD $3.7 million.
Near-term Anticipated Milestones

Interim data from AWARE-1 breast cancer study – Q4 2019.
Complete enrollment in AWARE-1 breast cancer study – Q1 2020.
Initiate phase 2 study BRACELET-1 study in HR+ / HER2- mBC – Q1 2020.
Final data from AWARE-1 breast cancer study – Q2 2020.
Financial

At September 30, 2019, the company reported $12.3 million in cash and cash equivalents.
As at November 8, 2019, the company had an unlimited number of authorized common shares with 26,357,724 common shares issued and outstanding, 16,443,500 warrants exercisable into 1,730,894 common shares with a $9.025 strike price, 3,567,989 warrants with a US$0.90 strike price, and 1,577,230 options and share units.
Operating expense for the third quarter of 2019 was $1.8 million compared to $1.5 million in the third quarter 2018.
Research and development expense for the third quarter of 2019 was $1.6 million compared to $1.9 million in the third quarter 2018.
The net loss for the third quarter of 2019 was $3.5 million compared to $3.3 million in the third quarter 2018, which equates to a net loss of $0.16 per share in 2019 compared to a net loss of $0.20 per share in 2018.
Webcast and Conference Call

Management will host a conference call for Analysts and Institutional Investors at 5:00 pm ET, today, Tuesday, November 12, 2019. The live call may be accessed by dialing 844-407-9500 or callers in North America. Overseas callers should contact investor relations for the toll-free dial information for their country. A replay of this call will be available approximately two hours after the call is ended at (877)-481-4010, using the replay code 56787 and will be available for one week.

A live webcast of the call will be accessible on the Investor Relations page of Oncolytics’ website at www.oncolyticsbiotech.com and will be archived for three months.

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

On November 11, 2019 ASLAN Pharmaceuticals (Nasdaq:ASLN, TPEx:6497), a clinical-stage oncology and immunology focused biopharma company, reported topline data from the TreeTopp (TREatmEnT OPPortunity with varlitinib in biliary tract cancer) study in second line biliary tract cancer (BTC) patients (Press release, ASLAN Pharmaceuticals, NOV 11, 2019, View Source [SID1234550867]). Varlitinib did not met the primary endpoints of progression-free survival (PFS) and overall response rate (ORR) as assessed by ICR according to RECIST. The safety findings were consistent with the known profile of varlitinib.

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

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

                  Schedule Your 30 min Free Demo!

The global, double-blind, randomised two-arm study enrolled 127 patients, who had failed first line therapy, from 56 sites in the US, Europe, Japan, Australia and other Asian countries. The median PFS was 2.83 months for varlitinib in combination with capecitabine arm of the study versus median PFS of 2.79 in the control arm. ORR was 9.4% in the varlitinib arm versus 4.8% in the control arm.

Although the trial did not reach statistical significance, pre-planned exploratory analyses did identify a sub-group which appeared to show improved efficacy. This finding has been supported by retrospective review of the JADETREE study which tested varlitinib in combination with capecitabine in second line BTC patients in China. Further analysis of the data is ongoing.

Dr Carl Firth, Chief Executive Officer of ASLAN Pharmaceuticals, said: "The results from the study are disappointing. They will, however, provide the scientific community with important insights into an aggressive and under-researched disease that presents a growing burden of care worldwide as prevalence rises. I would like to extend our thanks to the patients, trial investigators and site personnel who participated in the study and to the ASLAN team for their commitment to the development of varlitinib. ASLAN remains focused on the promising molecules in its portfolio, including the ongoing study in atopic dermatitis of ASLAN004, our IL-13 receptor antibody which blocks signalling through IL-4 and IL-13. We look forward to the interim readout in early 2020."

About varlitinib

Varlitinib (ASLAN001) is a highly potent, oral, reversible, small molecule pan-HER inhibitor that targets the human epidermal growth factor receptors HER1, HER2 and HER4. These receptors can be mutated or overexpressed in many tumours, which can cause excessive proliferative activity and uncontrolled growth. Therefore, by inhibiting the activation of the HER receptors, varlitinib could inhibit proliferation and control tumour growth. Varlitinib has been granted orphan drug designation in the United States for gastric cancer and cholangiocarcinoma, a sub-type of biliary tract cancer, and was awarded orphan drug designation for the treatment of biliary tract cancer by the Ministry of Food and Drug Safety in South Korea. Varlitinib is currently being tested in combination with paclitaxel in an ongoing investigator-initiated phase 2 umbrella study in second line HER1/HER2 gastric cancer (the K-MASTER study).

On November 11, 2019 Zimmer Biomet Holdings, Inc. (NYSE and SIX: ZBH), a global leader in musculoskeletal healthcare, reported that it will participate in the Piper Jaffray Annual Healthcare Conference at the Lotte New York Palace in New York City (Press release, Zimmer Holdings, NOV 11, 2019, View Source [SID1234550883]). Bryan Hanson, President and Chief Executive Officer and Suky Upadhyay, Executive Vice President and Chief Financial Officer, will present for the company on Wednesday, December 4, 2019, at 11:30 a.m. Eastern Time.

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!

A live webcast of the presentation can be accessed via Zimmer Biomet’s Investor Relations website at https://investor.zimmerbiomet.com. The webcast will be archived for replay following the conference.

On November 11, 2019 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that its New Drug Application ("NDA") for surufatinib for the treatment of patients with advanced non-pancreatic neuroendocrine tumors ("NET") has been accepted for review by the China National Medical Products Administration (Press release, Hutchison China MediTech, NOV 11, 2019, View Source [SID1234551038]).

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

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

                  Schedule Your 30 min Free Demo!

The NDA is supported by data from the successful SANET-ep study, a Phase III study of surufatinib in advanced neuroendocrine tumors – extra-pancreatic patients in China for whom there is no effective therapy. The positive results of this trial were highlighted in an oral presentation at the 2019 European Society for Medical Oncology Congress on September 29, 2019.

Christian Hogg, Chief Executive Officer of Chi-Med commented, "This NDA filing puts us on track for the potential approval and launch of surufatinib in China, an important development for NET patients with limited treatment options. In order to maximize patient access to surufatinib upon regulatory approval, we are now building our own dedicated commercial oncology organization and expect to be ready to cover all relevant hospitals and clinics in China at the time of launch."

"We believe surufatinib has robust efficacy, tolerability and combinability with a dual angio-immuno kinase inhibition profile, which may make it an attractive treatment in China," Mr. Hogg added.

Chi-Med currently retains all worldwide rights to surufatinib. Surufatinib is under investigation in multiple solid tumors in China, the U.S. and Europe, both as a monotherapy and in combination with immunotherapies.

Surufatinib is Chi-Med’s second in-house discovered novel oncology drug to reach NDA submission in China, following the launch of fruquintinib last year for colorectal cancer under the brand name Elunate.

About Neuroendocrine Tumors (NET)

Neuroendocrine tumors form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant. Neuroendocrine tumors are typically classified as pancreatic neuroendocrine tumors or other neuroendocrine tumors. Approved targeted therapies include Sutent and Afinitor for pancreatic neuroendocrine tumors, or well-differentiated, non-functional gastrointestinal or lung neuroendocrine tumors.

According to Frost and Sullivan, there were 19,000 newly diagnosed cases of neuroendocrine tumors in the U.S. in 2018. Importantly, neuroendocrine tumors are associated with a relatively long duration of survival compared to other tumors. As a result, there were approximately 141,000 estimated patients living with neuroendocrine tumors in the U.S. in 2018 of which over 90%, or approximately 132,000, were non-pancreatic neuroendocrine tumor patients.

In China, there were approximately 67,600 newly diagnosed neuroendocrine tumor patients in 2018 and, considering the current incidence to prevalence ratio in China, potentially as many as 300,000 patients living with the disease in the country1. It is estimated that approximately 80% of the patients living with neuroendocrine tumors in China are non-pancreatic neuroendocrine tumor patients.

About SANET-ep

SANET-ep is a randomized, double-blind, placebo-controlled, multi-center, Phase III study comparing surufatinib orally daily with placebo in patients with low- or intermediate-grade advanced extra-pancreatic neuroendocrine tumors for whom there is no effective therapy. In June 2019, a 198 patient interim analysis was conducted, leading the Independent Data Monitoring

Committee (IDMC) to determine that the study met the pre-defined primary endpoint of progression-free survival ("PFS") and should be stopped early. 84% of the patients in the study had disease with pathological grade 2. 41% of patients had disease originating outside of the gastrointestinal (GI) tract and the lung or with unknown origin.

Surufatinib reduced the risk of progression or death by 67%. Median PFS per investigator assessment was 9.2 months for patients treated with surufatinib, as compared to 3.8 months for patients in the placebo group (hazard ratio [HR] 0.334; 95% confidence interval [CI] 0.223-0.499; p<0.0001). The efficacy of surufatinib was seen across all subgroups, and supported by statistically significant improvement as measured by secondary efficacy endpoints including objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DoR), safety, and tolerability. Efficacy was also supported by Blinded Independent Image Review Committee (BIIRC) assessment. Overall survival (OS) data was not mature, with only 18.7% OS events at data cut-off. The safety profile was consistent with observations in prior clinical studies. Additional details may be found at clinicaltrials.gov, using identifier NCT02588170.

About Surufatinib

Surufatinib (previously known as HMPL-012 or sulfatinib) is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptors ("VEGFR") and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies. Surufatinib is in several late-stage and proof-of-concept clinical trials in China and proof-of-concept clinical trials in the U.S.

According to Frost & Sullivan, the market for VEGF/VEGFR inhibitors in China has grown from US$500 million in 2015 to over US$1.5 billion in 2019 and is expected to reach US$5 billion by 2026.

Chi-Med currently retains all rights to surufatinib worldwide.

Pancreatic neuroendocrine tumors in China: In 2016, we initiated the SANET-p study, which is a pivotal Phase III study in patients with low- or intermediate-grade, advanced pancreatic neuroendocrine tumors in China. The primary endpoint is PFS. We expect an interim analysis in the first half of 2020 and enrollment to complete in 2020 (clinicaltrials.gov identifier: NCT02589821).

Neuroendocrine tumors in the U.S. and Europe: The encouraging data from the Phase II and Phase III studies of surufatinib in neuroendocrine tumors in China (clinicaltrials.gov identifier: NCT02267967), and the ongoing Phase Ib study in the U.S. (clinicaltrials.gov identifier: NCT02549937), have led us to decide to proceed with planning a registration study in neuroendocrine tumors patients.

Biliary tract cancer in China: In March 2019, we initiated a Phase IIb/III study comparing surufatinib with capecitabine in patients with advanced biliary tract cancer whose disease progressed on first-line chemotherapy. The primary endpoint is OS (clinicaltrials.gov identifier NCT03873532).

Immunotherapy combinations: In November 2018 and September 2019, we entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies. This included global collaborations to evaluate the combination of surufatinib with Tuoyi, approved in China by Shanghai Junshi Biosciences Co. Ltd, and with Tyvyt, approved in China by Innovent Biologics, Inc.