On November 4, 2019 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on developing curative cell therapies for cancer, reported a strategic shift to focus development on its ACTR and BOXR product candidates in solid tumors and supportive platform capabilities (Press release, Unum Therapeutics, NOV 4, 2019, View Source [SID1234550246]).

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"We are uniquely positioned to address the challenge of treating solid tumor cancers, and now is the time to focus our efforts, having recently validated our ACTR technology in the hematologic setting and with preclinical data emerging from BOXR1030, the first product candidate from our BOXR platform. Our ACTR technology enables selective T cell targeting for on-tumor attack, while our BOXR platform makes it possible to overcome solid tumor immunosuppression, the fundamental challenge that has limited the effectiveness of cell therapies," said Chuck Wilson Ph.D., President and Chief Executive Officer of Unum. "Our priorities in solid tumors include completing the ongoing Phase 1 trial of ACTR707 in HER2+ cancers; advancing BOXR1030 towards the clinic with an anticipated IND filing in 2020; and expanding our BOXR platform to accelerate discovery of new product candidates across a broad range of immune cell therapies, including both autologous and allogeneic approaches."

ACTR707 was engineered for properties that optimize its function in solid tumors including increased proliferation, cytokine secretion, and persistence. With Unum’s focus on developing therapies for solid tumors, the company will de-prioritize investment in its hematologic programs. Testing through the first four dose levels in the ongoing ATTCK-20-03 Phase 1 trial in non-Hodgkin lymphoma has now established proof-of-concept for ACTR707. Given favorable tolerability to date at relatively low doses, Unum is announcing today plans to continue limited dose escalation to inform potential future development of the program in 2020.

Separately, Unum and its partner, Seattle Genetics, Inc., have suspended further dose-escalation of the ATTCK-17-01 Phase 1 trial of ACTR087 with SEA-BCMA in multiple myeloma pending a further review of this program. No dose-limiting toxicities (DLTs) following ACTR087 administration were reported and no severe adverse events of cytokine release syndrome (CRS) or neurologic events have been observed to date.

Solid Tumor Program Highlights

Phase 1 ATTCK-34-01 Trial: ACTR707 combined with trastuzumab to treat advanced HER2+ solid tumor cancers. Five clinical sites are now activated to support the Phase 1 trial that is currently enrolling patients. Unum expects to report preliminary safety data from patients treated in the first dose cohort of the trial by the end of this year and to report safety and clinical response data from multiple dose cohorts in 2020.

BOXR1030: Incorporating the GOT2 transgene and targeting GPC3+ solid tumor cancers. Unum’s first product candidate selected from its Bolt-On Chimeric Receptor (BOXR) platform, BOXR1030, continues to progress towards first-in-human clinical trials. BOXR1030 expresses a glypican-3 (GPC3) targeted chimeric antigen receptor (CAR) and leverages the "bolt-on" transgene glutamic-oxaloacetic transaminase 2 (GOT2) to improve T cell function in the solid tumor microenvironment by enhancing T cell metabolism. Preclinical studies have characterized the mechanism of action of BOXR1030’s bolt-on transgene with further details to be presented at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) conference during November 6-10, 2019. Based on recent progress, Unum now plans to file an investigational new drug (IND) application for BOXR1030 in late 2020, enabling subsequent clinical testing in GPC3+ cancers.

BOXR Platform Expansion: Unum’s BOXR platform was established over two years ago with the aim of discovering novel transgenes that can be co-expressed with chimeric-targeting receptors to improve the function of T cells in the solid tumor microenvironment. As part of its strategic shift to target solid tumors, Unum will be scaling up its BOXR platform capabilities with the objectives of: (1) expanding the scope of biological mechanisms and transgenes in its proprietary BOXR library, (2) enabling BOXR bolt-on applications for a broad range of immune cell therapies, including both autologous and allogeneic approaches, and (3) advancing new BOXR product candidates into the clinic.
Hematologic Program Highlights

Phase 1 ATTCK-20-03 trial: ACTR707 combined with rituximab for relapsed/refractory non-Hodgkin lymphoma. As a preliminary update provided today for the six patients treated in Cohort 4 (80M ACTR707+ T cells), complete response was achieved at the first response assessment in two of six patients as of the October 2019 analysis, yielding a complete response rate of 40% (eight of 20 patients) in Cohorts 1 through 4. Of the eight complete responders, four remained in complete response at six months of follow-up, two remain in complete response but have not yet reached the six-month timepoint for evaluation, and two progressed before the six-month timepoint. In Cohorts 1 through 4, ACTR707 was well-tolerated in combination with rituximab. No DLTs, no adverse events of CRS, and no severe neurological adverse events including neurotoxicity have been reported as of the October 2019 cutoff. Further results will be presented at the American Society for Hematology (ASH) (Free ASH Whitepaper) Annual Meeting during December 7-10, 2019. Unum plans to enroll up to two additional cohorts (three to four patients per cohort) in the trial, escalating the maximum dose up to 180M ACTR707+ T cells. With patient screening and planned dosing underway, Unum plans to report preliminary results from this dose escalation during 2020. The ability to differentiate on both efficacy and safety relative to currently available therapies and those in development from these additional cohorts will drive a decision during 2020 whether to advance the program into an expanded dose cohort and potential pivotal studies.

Phase 1 ATTCK-17-01 trial: ACTR087 combined with SEA-BCMA for relapsed/refractory multiple myeloma. Two additional cohorts of patients have been treated in the Phase 1 trial in 2019, escalating doses of the SEA-BCMA antibody to 2.0 mg/kg and of the ACTR087+ T cells to 50M. Unum and Seattle Genetics have suspended further dose-escalation of the trial and are reviewing the next steps with this program.
Investor Call and Webcast Information

Unum will host a live conference call and webcast today, November 4, 2019, at 4:30 p.m. ET, to discuss these company updates. To access the call, please dial 866-300-3411 (domestic) or 636-812-6658 (international) and refer to conference ID number 2177408. A webcast will be available at unumrx.com at least 10 minutes before the event begins. The archived webcast will be available at the same location approximately two hours after the event and will be archived for 90 days.

On November 4, 2019 Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported its financial and operational results for the third quarter ended September 30, 2019 (Press release, Sierra Oncology, NOV 4, 2019, View Source [SID1234550245]).

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"During the third quarter, we continued to prepare for the launch of the MOMENTUM Phase 3 clinical trial, which is expected to occur in the fourth quarter of 2019. Data that will be generated from this trial, along with data from more than 800 myelofibrosis patients previously treated with momelotinib, many of them durably benefiting for several years of treatment, will form the basis of our planned regulatory submissions for this drug," said Dr. Nick Glover, President and CEO of Sierra Oncology. "If ultimately approved, momelotinib could represent a significant addition to the limited number of therapeutics available to patients with myelofibrosis, and potentially become the first therapeutic capable of improving anemia in these patients rather than exacerbating it, while also providing meaningful and long-lasting symptom and spleen benefits."

Sierra’s pipeline also includes a portfolio of DNA Damage Response (DDR) assets, SRA737 (Chk1 inhibitor) and SRA141 (Cdc7 inhibitor). Sierra has previously announced plans to prioritize its resources on the development of momelotinib and has launched a campaign exploring non-dilutive strategic options to support the future continued development of these other drug candidates.

About the MOMENTUM Phase 3 Clinical Trial for Patients with Myelofibrosis:

Sierra plans to launch the MOMENTUM Phase 3 clinical trial in the fourth quarter of 2019. The randomized double-blind trial is designed to enroll 180 myelofibrosis patients who are symptomatic and anemic, and who have been treated previously with a JAK inhibitor. Patients will be randomized 2:1 to receive either momelotinib or danazol. Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients, as recommended by NCCN and ESMO (Free ESMO Whitepaper) guidelines. After 24 weeks of treatment, patients on danazol will be allowed to crossover to receive momelotinib.

The Primary Endpoint of the trial is the Total Symptom Score (TSS) response rate of momelotinib compared to danazol at Week 24 (99% power; p-value < 0.05).

Secondary and exploratory endpoints include:

Transfusion Independence (TI) rate at Week 24 (key secondary: >90% powered; p-value < 0.05),

Splenic response rate (SRR) at Week 24 (>90% powered; p-value < 0.05),

Duration of TSS response to Week 48,

Other measures of anemia benefit, including Transfusion Dependence response rate and various measures of cumulative transfusion burden,

Patient Reported Outcome measures of fatigue and physical function.

Dr. Srdan Verstovsek, MD, PhD, Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, has been named Chief Investigator of the MOMENTUM Phase 3 trial.

The FDA has granted Fast Track designation to momelotinib for the treatment of patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor.

Third Quarter 2019 Financial Results (all amounts reported in U.S. currency)

Research and development expenses were $10.1 million for the three months ended September 30, 2019, compared to $12.9 million for the three months ended September 30, 2018. The decrease was due to a $3.0 million upfront fee paid to Gilead to acquire momelotinib in the third quarter of 2018 and decreases in SRA737 and SRA141 costs, including a $2.4 million decrease in clinical trial costs primarily related to SRA737, a $1.4 million decrease in third-party manufacturing costs, and a $0.5 million decrease in research and preclinical costs. These decreases were partially offset by costs pertaining to momelotinib including an increase of $3.9 million in clinical trial and development related costs and a $0.6 million increase in third-party manufacturing costs. Research and development expenses included non-cash stock-based compensation of $0.9 million and $1.2 million for the three months ended September 30, 2019 and 2018, respectively.

Research and development expenses were $32.0 million for the nine months ended September 30, 2019, compared to $30.0 million for the nine months ended September 30, 2018. The increase was primarily due to costs related to momelotinib including a $8.2 million increase in clinical trial and development costs, a $1.9 million increase in third-party manufacturing costs and a $2.1 million increase in personnel-related and allocated overhead costs. These increases were partially offset by a $3.0 million upfront fee paid to Gilead to acquire momelotinib in the third quarter of 2018 and decreases in SRA737 and SRA141 costs, including a $3.6 million decrease in third-party manufacturing costs, a $2.4 million decrease in clinical trial costs primarily related to SRA737, and a $1.3 million decrease in research and preclinical costs. Research and development expenses included non-cash stock-based compensation of $3.3 million for the nine months ended September 30, 2019 and 2018.

General and administrative expenses were $3.1 million for both the three months ended September 30, 2019 and 2018. General and administrative expenses included non-cash stock-based compensation of $0.4 million and $0.7 million for the three months ended September 30, 2019 and 2018, respectively.

General and administrative expenses were $10.0 million for the nine months ended September 30, 2019, compared to $10.7 million for the nine months ended September 30, 2018. This decrease was due to decreases in personnel-related and allocated overhead costs of $0.3 million, professional fees of $0.2 million and business development related costs of $0.2 million. General and administrative expenses included non-cash stock-based compensation of $1.5 million and $1.8 million for the nine months ended September 30, 2019 and 2018, respectively.

For the three months ended September 30, 2019, Sierra incurred a net loss of $12.9 million compared to a net loss of $15.6 million for the three months ended September 30, 2018. For the nine months ended September 30, 2019, Sierra incurred a net loss of $40.8 million compared to a net loss of $39.1 million for the nine months ended September 30, 2018.

Cash and cash equivalents totaled $67.7 million as of September 30, 2019, compared to $106.0 million as of December 31, 2018. At September 30, 2019, there were 74,688,283 shares of common stock issued and outstanding, an additional 13,222,900 issuable upon exercise of stock options and warrants, and a term loan of $5.0 million.

On November 4, 2019 Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported its financial and operational results for the third quarter ended September 30, 2019 (Press release, Sierra Oncology, NOV 4, 2019, View Source [SID1234550244]).

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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

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"During the third quarter, we continued to prepare for the launch of the MOMENTUM Phase 3 clinical trial, which is expected to occur in the fourth quarter of 2019. Data that will be generated from this trial, along with data from more than 800 myelofibrosis patients previously treated with momelotinib, many of them durably benefiting for several years of treatment, will form the basis of our planned regulatory submissions for this drug," said Dr. Nick Glover, President and CEO of Sierra Oncology. "If ultimately approved, momelotinib could represent a significant addition to the limited number of therapeutics available to patients with myelofibrosis, and potentially become the first therapeutic capable of improving anemia in these patients rather than exacerbating it, while also providing meaningful and long-lasting symptom and spleen benefits."

Sierra’s pipeline also includes a portfolio of DNA Damage Response (DDR) assets, SRA737 (Chk1 inhibitor) and SRA141 (Cdc7 inhibitor). Sierra has previously announced plans to prioritize its resources on the development of momelotinib and has launched a campaign exploring non-dilutive strategic options to support the future continued development of these other drug candidates.

About the MOMENTUM Phase 3 Clinical Trial for Patients with Myelofibrosis:

Sierra plans to launch the MOMENTUM Phase 3 clinical trial in the fourth quarter of 2019. The randomized double-blind trial is designed to enroll 180 myelofibrosis patients who are symptomatic and anemic, and who have been treated previously with a JAK inhibitor. Patients will be randomized 2:1 to receive either momelotinib or danazol. Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients, as recommended by NCCN and ESMO (Free ESMO Whitepaper) guidelines. After 24 weeks of treatment, patients on danazol will be allowed to crossover to receive momelotinib.

The Primary Endpoint of the trial is the Total Symptom Score (TSS) response rate of momelotinib compared to danazol at Week 24 (99% power; p-value < 0.05).

Secondary and exploratory endpoints include:

Transfusion Independence (TI) rate at Week 24 (key secondary: >90% powered; p-value < 0.05),
Splenic response rate (SRR) at Week 24 (>90% powered; p-value < 0.05),
Duration of TSS response to Week 48,
Other measures of anemia benefit, including Transfusion Dependence response rate and various measures of cumulative transfusion burden,
Patient Reported Outcome measures of fatigue and physical function.
Dr. Srdan Verstovsek, MD, PhD, Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, has been named Chief Investigator of the MOMENTUM Phase 3 trial.

The FDA has granted Fast Track designation to momelotinib for the treatment of patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor.

Third Quarter 2019 Financial Results (all amounts reported in U.S. currency)

Research and development expenses were $10.1 million for the three months ended September 30, 2019, compared to $12.9 million for the three months ended September 30, 2018. The decrease was due to a $3.0 million upfront fee paid to Gilead to acquire momelotinib in the third quarter of 2018 and decreases in SRA737 and SRA141 costs, including a $2.4 million decrease in clinical trial costs primarily related to SRA737, a $1.4 million decrease in third-party manufacturing costs, and a $0.5 million decrease in research and preclinical costs. These decreases were partially offset by costs pertaining to momelotinib including an increase of $3.9 million in clinical trial and development related costs and a $0.6 million increase in third-party manufacturing costs. Research and development expenses included non-cash stock-based compensation of $0.9 million and $1.2 million for the three months ended September 30, 2019 and 2018, respectively.

Research and development expenses were $32.0 million for the nine months ended September 30, 2019, compared to $30.0 million for the nine months ended September 30, 2018. The increase was primarily due to costs related to momelotinib including a $8.2 million increase in clinical trial and development costs, a $1.9 million increase in third-party manufacturing costs and a $2.1 million increase in personnel-related and allocated overhead costs. These increases were partially offset by a $3.0 million upfront fee paid to Gilead to acquire momelotinib in the third quarter of 2018 and decreases in SRA737 and SRA141 costs, including a $3.6 million decrease in third-party manufacturing costs, a $2.4 million decrease in clinical trial costs primarily related to SRA737, and a $1.3 million decrease in research and preclinical costs. Research and development expenses included non-cash stock-based compensation of $3.3 million for the nine months ended September 30, 2019 and 2018.

General and administrative expenses were $3.1 million for both the three months ended September 30, 2019 and 2018. General and administrative expenses included non-cash stock-based compensation of $0.4 million and $0.7 million for the three months ended September 30, 2019 and 2018, respectively.

General and administrative expenses were $10.0 million for the nine months ended September 30, 2019, compared to $10.7 million for the nine months ended September 30, 2018. This decrease was due to decreases in personnel-related and allocated overhead costs of $0.3 million, professional fees of $0.2 million and business development related costs of $0.2 million. General and administrative expenses included non-cash stock-based compensation of $1.5 million and $1.8 million for the nine months ended September 30, 2019 and 2018, respectively.

For the three months ended September 30, 2019, Sierra incurred a net loss of $12.9 million compared to a net loss of $15.6 million for the three months ended September 30, 2018. For the nine months ended September 30, 2019, Sierra incurred a net loss of $40.8 million compared to a net loss of $39.1 million for the nine months ended September 30, 2018.

Cash and cash equivalents totaled $67.7 million as of September 30, 2019, compared to $106.0 million as of December 31, 2018. At September 30, 2019, there were 74,688,283 shares of common stock issued and outstanding, an additional 13,222,900 issuable upon exercise of stock options and warrants, and a term loan of $5.0 million.

On November 4, 2019 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that Alan H. Auerbach, Chairman, Chief Executive Officer, President and Founder of Puma, will provide an overview of the Company at 10:55 a.m. MST (9:55 a.m. PST, 12:55 p.m. EST) on Tuesday, November 12, at the Credit Suisse 28th Annual Healthcare Conference (Press release, Puma Biotechnology, NOV 4, 2019, View Source [SID1234550243]). The conference will be held at The Phoenician Resort in Scottsdale, Arizona.

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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

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A live webcast of the presentation will be available on the Company’s website at www.pumabiotechnology.com. The presentation will be archived on the website and available for 30 days.

On November 4, 2019 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that it is closer to submitting an Investigational New Drug application (IND) to the U.S. Food & Drug Administration (FDA) (Press release, PharmaCyte Biotech, NOV 4, 2019, View Source [SID1234550242]). PharmaCyte and its partner, Austrianova Singapore (Austrianova), has successfully completed encapsulation of the cells from PharmaCyte’s Master Cell Bank (MCB) in the second of two staggered and back-to-back manufacturing runs for the production of PharmaCyte’s clinical trial product. This product will be used for PharmaCyte’s planned clinical trial in patients with locally advanced, inoperable pancreatic cancer (LAPC).

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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

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PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, commented, "The encapsulation process was performed last week at Austrianova’s manufacturing facility in Thailand. After reviewing the first pictures of the encapsulated cells, we’re confident that this manufacturing run is progressing as well as our first successful manufacturing run.

"We are anxiously awaiting the completion of the second of the two back-to-back manufacturing runs and the results from the FDA required testing on each of those runs. Once the information from that testing is available, it will be incorporated into our Investigational New Drug application (IND) for submission to the FDA."

Most of the work needed for PharmaCyte to submit an IND to the FDA has been completed. The rate limiting factor is and always has been for Austrianova to complete successfully two back-to-back manufacturing runs. During PharmaCyte’s recent shareholder update call, the company reported on Austrianova’s work to encapsulate successfully PharmaCyte’s genetically modified human cells that will be used to treat patients suffering from LAPC.

After months of extensive research and development (R&D) by a team of experts from Austrianova and PharmaCyte, a total of eight different changes were made to the manufacturing process. It was not until the eighth and final change was made that the encapsulated cells grew as well in Austrianova’s manufacturing facility in Thailand as they grew at Austrianova’s R&D facility in Singapore.

Once the recently encapsulated cells in this second of two manufacturing runs have completely filled the capsules, they will be placed into PharmaCyte’s clinical trial syringes and then frozen. A representative sample of those syringes will be thawed and undergo the FDA required "release testing." All "release testing" related to safety of the encapsulated cells is being outsourced by PharmaCyte to independent third-party laboratories in Europe. All "release testing" related to functionality of the encapsulated cells is being handled by Austrianova at its GMP facility in Thailand.

To learn more about PharmaCyte’s pancreatic cancer treatment and how it works inside the body to treat locally advanced inoperable pancreatic cancer, the company encourages you to watch its documentary video complete with medical animations at: View Source