On August 9, 2021 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery and development of drugs for the treatment of cancer, reported financial results for the second quarter ended June 30, 2021 and provided a corporate update (Press release, Cellectar Biosciences, AUG 9, 2021, View Source [SID1234586147]).

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Second Quarter and Recent Corporate Highlights

Announced the expansion of the ongoing collaboration with biotechnology company IntoCell Inc., combining their novel linker chemistry with Cellectar’s validated targeting platform to create novel next generation phospholipid drug conjugate (PDC) therapeutics.

Announced a co-development and commercialization collaboration with LegoChemBio, a clinical stage biotechnology company to utilize their proprietary drug conjugate linker-toxin platform to further enhance the company’s portfolio of next generation PDC therapeutics.

Presented a poster entitled "Treatment Free Remission (TFR) and Overall Response Rate (ORR) Results in Patients with Relapsed/Refractory Waldenstrom’s Macroglobulinemia (WM) Treated with CLR 131" at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting.

The poster provided an update of six patients from the company’s Phase 2a study of CLR 131 in Waldenstrom’s macroglobulinemia demonstrating encouraging data.
A 100% (6/6) overall response rate, 83.3% (5/6) major response rate and a 16.7% (1/6) complete response rate.
A median time to initial response of 22 days after first infusion with a median time to major response, as defined as at least a 50% reduction in IgM, of 44 days after first infusion.
A mean treatment free remission, as defined as the time from the last CLR 131 infusion to progression of disease, of 1.1 years and ongoing.
Median duration of response had not been reached, with 100% of the MYD88 wild type and high-risk patients exceeding 8.5 months.
Progression free survival (PFS) for both MYD88 wild type patients as well as the high-risk subgroup had not been reached after 18 months; PFS for the multi-drug refractory patients subgroup was 11 months.

Hosted Key Thought Leader event with Dr. Sikander Ailawadhi, M.D., of the Mayo Clinic, the lead investigator for the company’s pivotal study of CLR 131 in patients with Waldenstrom’s macroglobulinemia.

Added extensive hematology and oncology expertise to the company’s board of directors with the addition of Dr. Asher Alban Chanan-Khan as an independent director.
"During the second quarter, we remained focused on advancing both our preclinical and clinical objectives. The high level of interest and participation in our WM pivotal study by international thought leadership and academic centers from around the globe is extremely exciting," said James Caruso, president and CEO of Cellectar. "We presented compelling CLR 131 data at ASCO (Free ASCO Whitepaper) and announced two new collaborations with biotechnology companies specializing in proprietary drug conjugate linker chemistry to diversify our PDC pipeline. With over $46 million in cash and cash equivalents as of June 30, 2021, we are well capitalized with the cash runway to execute on our anticipated value enhancing milestones into 2023."

Second Quarter Financial Highlights

Cash and Cash Equivalents: As of June 30, 2021, the company had cash and cash equivalents of $46.8 million compared to $57.2 million at December 31, 2020. Cash used in operating activities was approximately $11.6 million during the six months ended June 30, 2021 as compared to $6.6 million during the six months ended June 30, 2020.

Research and Development Expense: R&D expense for the three months ended June 30, 2021 was $4.6 million, compared to $2.5 million for the three months ended June 30, 2020. The cumulative R&D spending for the first six months of 2021 was $9.3 million as compared to $5.1 million for the first six months of 2020. The increase in R&D expense year-to-date in 2021 was primarily a result of an increase related to start-up costs for our WM pivotal study and other clinical project costs and general research and development costs offset by lower manufacturing and related costs.
General and Administrative Expense: G&A expense for the three months ended June 30, 2021 was $1.4 million compared to $1.2 million for the three months ended June 30, 2020. The cumulative G&A spending for the first six months of 2021 were of $3.1 million as compared to $2.5 million for the first six months of 2020. The increase in G&A expense year-to-date in 2021 was primarily a result of an increase in professional fees, insurance and personnel costs.

Net Loss: The net loss attributable to common stockholders for the three months ended June 30, 2021 was ($6.0) million, or ($0.11) per share, compared to ($3.6) million, or ($0.26) per share, in 2020. Net loss attributable to common stockholders for the six months ended June 30, 2021 was ($12.4) million, or ($0.25) per share, compared to ($7.6) million, or ($0.65) per share, in 2020.

On August 9, 2021 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported that the Independent Data Monitoring Committee for the ENVASARC pivotal trial has recommended that the trial proceed as planned following the review of 12 week safety data from more than 20 patients enrolled into the trial as of May 2021 (Press release, Tracon Pharmaceuticals, AUG 9, 2021, View Source [SID1234586145]). The safety data reviewed included data from more than 10 patients enrolled into cohort A of treatment with single agent envafolimab and more than 10 patients enrolled into cohort B of treatment with envafolimab and Yervoy (ipilimumab).

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"Envafolimab continues to be well tolerated as a single agent and when combined with Yervoy in refractory sarcoma patients who are enrolled in the ENVASARC trial. We remain on track for the Independent Data Monitoring Committee to review interim efficacy data in the fourth quarter of this year," said James Freddo, M.D., TRACON’s Chief Medical Officer.

About Envafolimab

Envafolimab (KN035), a novel, single-domain antibody against PD-L1, is the first subcutaneously injected PD-(L)1 inhibitor to be studied in pivotal trials. Envafolimab is currently being studied in the ENVASARC Phase 2 pivotal trial in the U.S. sponsored by TRACON, has been studied in a completed Phase 2 pivotal trial as a single agent in MSI-H/dMMR advanced solid tumor patients in China and is being studied in an ongoing Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China, with both Chinese trials sponsored by 3D Medicines. TRACON’s partners Alphamab Oncology and 3D Medicines submitted an NDA to the NMPA in China for envafolimab in MSI-H/dMMR cancer that was accepted for review in December 2020 and granted priority review in January 2021. In the Phase 2 MSI-H/dMMR advanced solid tumor trial, the confirmed objective response rate (ORR) by blinded independent central review in MSI-H/dMMR colorectal cancer (CRC) patients treated with envafolimab who failed a fluoropyrimidine, oxaliplatin and irinotecan was 32%, which was similar to the 28% confirmed ORR reported in the Opdivo package insert in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin, and irinotecan and the 33% confirmed ORR reported for Keytruda in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin and irinotecan in cohort A of the KEYNOTE-164 clinical trial.

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at approximately 25 top cancer centers in the United States that began dosing in December 2020. TRACON expects the trial to enroll 160 patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor, with 80 patients enrolled into cohort A of treatment with single agent envafolimab and 80 patients enrolled into cohort B of treatment with envafolimab and Yervoy. The primary endpoint is ORR by blinded independent central review with duration of response a key secondary endpoint.

On August 9, 2021 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported that financial results for the second quarter ended June 30, 2021 were filed with the SEC on August 6, 2021 and provided a business update (Press release, Enlivex Therapeutics, AUG 9, 2021, View Source [SID1234586144]).

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"We are very pleased with our recent progress, which has placed us on track to achieve a steady cadence of value creating milestones," said Oren Hershkovitz, CEO of Enlivex. "Our placebo-controlled Phase IIb sepsis trial is ongoing, with top-line data expected in the second quarter of 2022. We are also on track to initiate a Phase IIb trial evaluating AllocetraTM as a treatment for severe/critical COVID-19 patients in Israel in Q3 of this year, and we plan to expand the trial to include European sites thereafter. These trials are each supported by compelling clinical data that highlight the broad applicability of Allocetra’s immunotherapeutic mechanism of action."

Dr. Hershkovitz continued, "Alongside our clinical progress, we have also generated preclinical data highlighting Allocetra’s potential to synergistically enhance the efficacy of cancer therapies. By combining AllocetraTM with these therapies, we believe we can improve response rates and provide effective therapeutic options to patients who currently have none available. We look forward to evaluating this hypothesis through our planned Phase Ib solid tumor trial. With a strong financial position and talented leadership team, we believe we are well positioned to advance these and our other clinical studies as we work to become a leader in cell therapies for infectious, inflammatory and oncologic diseases."

Business Highlights and Upcoming Milestones

Sepsis:

Sepsis is a life-threatening disease with no FDA approved therapies and a high unmet need. Each year, more than 1.7 million adults in the United States develop sepsis, with more than 270,000 dying of the disease. Enlivex’s immunotherapy product candidate AllocetraTM is being evaluated in a placebo-controlled, randomized, dose-finding, multi-center, Phase IIb trial in patients with pneumonia-associated sepsis. The trial, which has multiple sites currently open for enrollment, is expected to include 120 to 160 patients across four cohorts receiving varying doses of AllocetraTM or placebo, all in addition to standard-of-care therapy. The trial’s two primary endpoints include both safety (number and severity of adverse events and severe adverse events), and efficacy (change from baseline in sequential organ failure (SOFA) score) assessments throughout a 28-day follow-up period. The trial is supported by previously reported positive results from a Phase Ib investigator-initiated trial showing vastly improved clinical outcomes, including SOFA scores, duration of hospitalization, and mortality, in AllocetraTM-treated sepsis patients compared to a group of matched historical controls that received standard-of-care therapy. Top-line results from the Phase IIb study are expected in Q2 2022.

COVID-19:

Enlivex believes that COVID-19 will migrate from a pandemic to an endemic, with multiple variants continuing to circulate throughout the population. Further, AllocetraTM has demonstrated the potential to address a critical unmet need for COVID-19 patients in severe or critical condition, who don’t have many effective treatment options available today. In late 2020 and early 2021, Enlivex reported positive top-line results in 21 patients from Phase Ib and Phase II investigator-initiated trials in COVID-19 patients in severe/critical condition. Aggregate data from the two trials showed a 0% (0/21) mortality rate at the end of the 28 days follow-up period and that 90.5% (19/21) of patients recovered from their respective severe/critical condition and were discharged from the hospital after an average of 5.6 days following AllocetraTM administration.
To facilitate the advancement of its COVID-19 program, Enlivex has submitted a regulatory filing with the Israeli Ministry of Health to initiate a placebo-controlled, double-blinded, randomized, multi-center Phase IIb trial in COVID-19 patients in severe/critical condition with associated acute respiratory distress syndrome (ARDS). The trial will be designed to recruit up to 152 patients (76 AllocetraTM plus standard-of-care, 76 placebo plus standard-of-care). In addition, the Company plans to add several European clinical sites as part of this study, and is in discussions with the European Medicines Agency (EMA) and certain local European regulators for this purpose. The Phase IIb clinical trial will have two primary endpoints: ventilation-free survival and recovery for each of the two sub-populations of patients in the study (severe and critical), and could potentially be sufficient for obtaining emergency or conditional marketing authorization for either patient sub-population, though no guidance as per the potential for such emergency or conditional marketing authorization has been provided by the Israeli Ministry of Health or European regulators.

Solid tumors:

Alongside some industry experts, Enlivex believes that one of the main problems with the lack of efficacy of immunotherapies targeted at patients with various solid tumor malignancies is the negative reprogramming of macrophages in the tumor microenvironment. This negative reprogramming results in proliferation of pro-tumor macrophages, contributing to drug resistance, preventing disease resolution, and promoting disease severity. Data from initial preclinical solid tumor models suggest that AllocetraTM has the potential to reprogram such macrophages back to their respective homeostatic state, and thereby may assist in disease resolution and offer patients that do not respond well to existing FDA-approved immunotherapies with an effective treatment option. Based on these and other data, Enlivex plans to initiate a Phase Ib trial evaluating AllocetraTM in combination with a chemotherapy in solid peritoneal tumors in Q4 2021, and a Phase Ib trial evaluating AllocetraTM in combination with an immune checkpoint inhibitor H1 2022.
Corporate:

Subsequent to the quarter end, Enlivex initiated the design and construction process for a new cGMP AllocetraTM manufacturing plant in Israel. The Company intends to use the additional manufacturing capacity to support ongoing clinical trials, future clinical trials and initial commercial production of AllocetraTM that may occur if it receives applicable regulatory approvals. The planned new facility will initially be approximately 17,000 square feet, and will have the ability to be expanded to approximately 21,500 square feet in the future.

Subsequent to the quarter end, Enlivex hired biotech-industry veteran Tzvi Palash as Project Lead to manage the design and construction of the Company’s new cGMP AllocetraTM manufacturing plant. Mr. Palash joined Enlivex from Gamida Cell, where he served as Chief Operating Officer.

In May 2021, Enlivex was awarded an Israel Innovation Authority (IIA) Grant of approximately $1.1 million to support the clinical development of AllocetraTM in sepsis. To date, the Company has received a total of approximately $7.6 million in non-dilutive grants from the IIA for clinical trials and product development, excluding this recently approved grant.

Throughout the second quarter, Enlivex’s global intellectual property portfolio around AllocetraTM was strengthened by the issuance of two patents. The first of these patents was granted in Canada (Canadian patent No. 2,893,962) and covers pharmaceutical compositions, manufacturing methods, and uses of AllocetraTM. The second patent, which was granted in Europe (European patent No. 3,258,943), covers therapeutic compositions of AllocetraTM and chimeric antigen receptor (CAR)-T immunotherapies for inhibition or reduction of cytokine storms associated with CAR-T therapies for cancer.
Second Quarter 2021 Financial Results

Research and development expenses were $2.539 million for the three months ended June 30, 2021, compared to $1.257 million for the same period in 2020. The increase was primarily attributable to increase in salaries, increase in expenses associated with pre-clinical studies, clinical studies and consumption of materials, and increase in stock-based compensation to employees offset by an increase in grants from the Israel Innovation Authority.

General and administrative expenses were $1.269 million for the three months ended June 30, 2021, compared to $0.976 million for the same period in 2020. The increase was primarily due to increase in stock-based compensation to employees and directors, and in insurance expenses.

Net loss for the three months ended June 30, 2021, was $3.108 million, compared to a net loss of $3.041 million for the three months ended June 30, 2020.

As of June 30, 2021, Enlivex had cash and marketable securities of $90.6 million. The Company believes that its existing cash and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements through 2023.
ABOUT ALLOCETRATM

AllocetraTM is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, COVID-19 and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, AllocetraTM has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

On August 9, 2021 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs, reported financial results for the three and six months ended June 30, 2021 and highlighted recent corporate updates (Press release, Heron Therapeutics, AUG 9, 2021, View Source [SID1234586143]).

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Recent Corporate Updates

Acute Care Franchise

ZYNRELEF Now Available: In May 2021, the U.S. Food and Drug Administration (FDA) approved the Company’s New Drug Application (NDA) for ZYNRELEF (bupivacaine and meloxicam) extended-release solution. ZYNRELEF is indicated for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. ZYNRELEF became commercially available in the U.S. on July 1, 2021. During the initial weeks of commercial launch, the reception to ZYNRELEF has been positive with 61 unique accounts already purchasing the product. The Company has applied for a unique C-code for ZYNRELEF, which would provide 3-year Medicare reimbursement outside the surgical bundle payment for outpatient procedures. In the interim, Medicare will reimburse ZYNRELEF under a miscellaneous C-code. In addition, multiple payers covering over 86 million commercial and Medicaid lives have already agreed to reimburse ZYNRELEF outside the surgical bundle payment for surgeries performed in ambulatory surgical centers, with many of these covered lives also having their hospital outpatient procedures reimbursed outside the surgical bundle payment.
NDA for HTX-019 for Prevention of PONV in Adults Planned in Late 2021: A 505(b)(2) NDA for HTX-019 for prevention of postoperative nausea and vomiting (PONV) in adults is on track for filing in late 2021.
Oncology Care Franchise

2021 Net Product Sales: For the three and six months ended June 30, 2021, oncology care franchise net product sales were $22.4 million and $42.5 million, respectively, compared to $22.7 million and $48.1 million, respectively, for the same periods in 2020. During the second quarter of 2021, the net product sales increased by 12% compared to the prior quarter and this increase was in-line with the 10% to 20% growth anticipated for the quarter. Heron continues to expect growth of the oncology care franchise net product sales, but at a slower rate than originally projected. Key factors influencing our growth rate projections are the lower rate of new cancer patient treatment starts due to the COVID-19 pandemic, fewer clinic anti-emetic administrations during the first half of 2021 compared to the prior year, stronger than expected competition, and the impact of value-based payer reimbursement.
CINVANTI Net Product Sales: Net product sales of CINVANTI (aprepitant) injectable emulsion for the three and six months ended June 30, 2021 were $19.7 million and $38.2 million, respectively, compared to $22.6 million and $47.8 million, respectively, for the same periods in 2020. During the second quarter of 2021, CINVANTI demand units increased by 22% over the prior quarter, which was partially offset by a lower net selling price.
SUSTOL Net Product Sales: Net product sales of SUSTOL (granisetron) extended-release injection for the three and six months ended June 30, 2021 were $2.7 million and $4.3 million, respectively, compared to $0.1 million and $0.3 million, respectively, for the same periods in 2020. During the second quarter of 2021, SUSTOL demand units increased by 108% over the prior quarter, which was partially offset by a lower net selling price.
2021 Oncology Care Franchise Net Product Sales Guidance: Heron currently expects third quarter of 2021 net product sales for the oncology care franchise to increase approximately 5% to 10% compared to the prior quarter. The Company is withdrawing its full-year 2021 net product sales guidance for the oncology care franchise based on the uncertainty associated with the rate of new cancer patient treatment starts and the impact of value-based contracting reimbursement.
"The reception in the marketplace for ZYNRELEF has been outstanding, with a large number of ordering accounts for the first weeks of a launch. Another important accomplishment in these first weeks of launch has been securing an unprecedented number of commercial and Medicaid payers agreeing to reimburse ZYNRELEF outside the surgical bundled payment. We are currently working with the FDA to determine the requirements to expand the drug’s label for use in additional indications," said Barry Quart, Pharm.D., Chairman and Chief Executive Officer of Heron. "For the oncology care franchise, our net product sales for the first half of 2021 were $42.5 million, and we expect sales for CINVANTI and SUSTOL to continue to grow in the second half of the year. In addition, we continue to advance HTX-019 and remain on track to submit an NDA to the FDA for PONV prevention in Q4 2021."

Financial Results

Net product sales for the three and six months ended June 30, 2021 were $22.4 million and $42.5 million, respectively, compared to $22.7 million and $48.1 million, respectively, for the same periods in 2020.

Heron’s net loss for the three and six months ended June 30, 2021 was $61.0 million and $113.6 million, or $0.62 per share and $1.20 per share, respectively, compared to $55.2 million and $106.8 million, or $0.61 per share and $1.18 per share, respectively, for the same periods in 2020. Net loss for the three and six months ended June 30, 2021 included non-cash, stock-based compensation expense of $11.2 million and $22.7 million, respectively, compared to $11.1 million and $23.1 million, respectively, for the same periods in 2020.

As of June 30, 2021, Heron had cash, cash equivalents and short-term investments of $257.7 million, compared to $208.5 million as of December 31, 2020. Net cash used for operating activities for the six months ended June 30, 2021 was $104.9 million, compared to $90.2 million for the same period in 2020. The increase in our net cash used for operating activities was primarily due to changes in working capital to prepare for the launch of ZYNRELEF in July 2021, including manufacturing of commercial inventory. We expect our net cash used for operating activities to moderate later this year.

About ZYNRELEF for Postoperative Pain

ZYNRELEF is the first and only dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first modified-release local anesthetic to be classified by FDA as an "extended-release" product because ZYNRELEF is also the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and significantly increased proportion of patients requiring no opioids through the first 72 hours following surgery compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. ZYNRELEF was approved by the FDA in May 2021 for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. In September 2020, the European Commission granted a marketing authorization for ZYNRELEF for the treatment of somatic postoperative pain from small- to medium-sized surgical wounds in adults. As of January 1, 2021, ZYNRELEF is approved in 31 European countries including the countries of the European Union and European Economic Area and the United Kingdom.

Please see full prescribing information, including Boxed Warning, at www.ZYNRELEF.com.

About HTX-019 for PONV

HTX-019 is an IV injectable emulsion formulation designed to directly deliver aprepitant, the active ingredient in EMEND (aprepitant) capsules, which is the only substance P/neurokinin-1 (NK1) receptor antagonist (RA) to be approved in the U.S. for the prevention of PONV in adults. The FDA-approved dose of oral EMEND is 40 mg for PONV, which is given within 3 hours prior to induction of anesthesia for surgery. In a Phase 1 clinical trial, 32 mg of HTX-019 as a 30-second IV injection was demonstrated to be bioequivalent to oral aprepitant 40 mg.

About CINVANTI for Chemotherapy Induced Nausea and Vomiting (CINV) Prevention

CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, an NK1 RA. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the U.S. prescribing information for CINVANTI is a 30-minute IV infusion or a 2-minute IV injection.

Please see full prescribing information at www.CINVANTI.com.

About SUSTOL for CINV Prevention

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-hydroxytryptamine type 3 RA that utilizes Heron’s Biochronomer drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy).

On August 9, 2021 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics, reported second quarter 2021 financial results and provided a business update (Press release, Rubius Therapeutics, AUG 9, 2021, View Source [SID1234586142]).

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"During the quarter, we continued to make excellent progress in advancing our fully owned oncology pipeline," said Pablo J. Cagnoni, M.D., President and Chief Executive Officer. "Given the favorable emerging safety profile and promising initial clinical activity reported for RTX-240, we initiated a combination Phase 1 arm with pembrolizumab with the goal of providing benefit to patients with cancers that have relapsed or are refractory after treatment with anti-PD-1 or PD-L1 antibodies."

"Bolstered by the promising clinical activity and safety reported as part of the initial data results in March 2021, and no dose-limiting toxicities observed to date, we are continuing to explore the dose and schedule in new cohorts in the Phase 1 arm of single-agent RTX-240 in advanced solid tumors," said Christina Coughlin, M.D., Ph.D., Chief Medical Officer. "We plan to present a comprehensive clinical data set from the trial, including data from the new cohorts and longer follow up for all patients."

Second Quarter 2021 and Recent Highlights

Strengthened Leadership Team

Dannielle Appelhans was appointed chief operating officer. She will oversee corporate strategy and technical operations. Dannielle brings significant experience in building organizations as they evolve from early- to late-stage development, with a particular focus on clinical and commercial manufacturing and scaling supply chains.

Single-Agent RTX-240 Phase 1/2 Clinical Trial for Advanced Solid Tumors

During the second quarter, two additional cohorts were added to explore the dose of RTX-240 with a more frequent schedule of administration in the Phase 1 single-agent arm in solid tumors. Enrollment in these cohorts continues.
The changes in dose and schedule are supported by initial clinical activity, safety data and no dose-limiting toxicities observed to date along with additional emerging data from dose escalation in the Phase 1 study.
The Company currently plans to present comprehensive results from this study at the end of 2021 or during the first quarter of 2022.
The Company presented preliminary safety and efficacy data from RTX-240 Phase 1/2 clinical trial for advanced solid tumors at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting on April 10, 2021.
The initial safety (n=16) and efficacy (n=15) findings, based on RECIST v1.1., with a data cutoff of February 28, 2021, demonstrated favorable emerging safety results across dose levels with no treatment-related Grade 3/4 adverse events or dose-limiting toxicities.
Single-agent activity was demonstrated with two partial responses (1 confirmed and 1 unconfirmed) and six patients with stable disease.
RTX-240 stimulated innate and adaptive immunity as demonstrated by the activation and expansion of NK or memory CD8+ T cells in all patients, with 9/16 patients showing activation and expansion in both cell types.
Additionally, trafficking data was separately reported as part of the initial data readout on March 15, 2021, which noted that immune cell trafficking of activated NK and T cells into the tumor microenvironment (TME) was observed in two solid tumor biopsies and one acute myeloid leukemia (AML) biopsy.
Phase 1 Arm in Ongoing Phase 1/2 RTX-240 Clinical Trial in Combination with KEYTRUDA (pembrolizumab) for Advanced Solid Tumors

The first patient was dosed with RTX-240 in combination with pembrolizumab for the treatment of patients with relapsed/refractory or locally advanced solid tumors in June 2021.
To be eligible for the trial, patients must have disease that is relapsed or refractory to an anti-PD-1 or PD-L1 therapy. The study continues to enroll additional patients.
With its mechanism of action as a broad immune agonist, RTX-240 may have synergy with immune checkpoint inhibition and potentially overcome resistance to PD-1 inhibition.
Preliminary data from single-agent RTX-240 Phase 1 study reported in March 2021, showed early evidence of favorable immune-permissive changes in the TME, including increased expression of PD-L1 and/or increased ratio of M1/M2 macrophages after treatment with RTX-240 in three out of four patient biopsies, suggesting single-agent RTX-240 is able to induce changes in the TME that have been associated with response to checkpoint inhibition.
Phase 1 Arm in Ongoing Phase 1/2 RTX-240 Clinical Trial in Relapsed/Refractory (R/R) Acute Myeloid Leukemia

RTX-240 is currently being evaluated as a single-agent in a Phase 1 arm of the ongoing Phase 1/2 clinical trial of RTX-240 in patients with R/R AML.
Based on the initial clinical and pharmacodynamic data observed in the single-agent solid tumor Phase 1 arm, the Company implemented a more frequent dose administration schedule and added an additional cohort in the R/R AML arm of the trial.
Dosing has been completed in the first four dose cohorts and enrollment in an additional dose cohort is expected to begin in the third quarter of 2021.
Given the mechanism of RTX-240 in activating and expanding NK and T cells and its preliminary favorable safety profile seen to date, RTX-240 could potentially provide benefit as a maintenance therapy for AML patients in remission following chemotherapy or stem cell transplantation.
RTX-321 Artificial Antigen-Presenting Cell (aAPC) Development Program for Human Papillomavirus (HPV) 16-Positive Cancers

Enrollment continues in the Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers, including cervical, head & neck cancers, and anal cancer.

Peer-Reviewed Publications and Poster Presentations at Medical Conferences

In July 2021, the manuscript entitled "Anti-Tumor Effects of RTX-240: an Engineered Red Blood Cell Expressing 4-1BB Ligand and Interleukin-15" was published in the peer-reviewed journal Cancer Immunology, Immunotherapy, highlighting preclinical findings for RTX-240, which demonstrated that RTX-240 activates and expands CD8+ T cells and NK cells in vitro and in vivo generating potent anti-tumor activity in both a colorectal and melanoma model.
In May 2021, the manuscript entitled, "Engineered Red Blood Cells as an Off-the-Shelf Allogeneic Anti-Tumor Therapeutic" was published in the peer-reviewed journal Nature Communications highlighting preclinical findings for RTX-321, which demonstrated that the surrogate of RTX-321 induced a broad immune response, epitope spreading and memory formation in preclinical models.
Preliminary safety and efficacy data from RTX-240 Phase 1/2 Clinical Trial for advanced solid tumors was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting on April 10, 2021.
Near-Term Catalysts and Operational Objectives

Present additional clinical data from the RTX-240 solid tumor Phase 1 clinical trial at the end of 2021 or during the first quarter of 2022;
Select specific solid tumor types that will be pursued in the Phase 2 expansion cohort of RTX-240;
Report initial clinical data from the Phase 1 arm of the RTX-240 clinical trial in relapsed/refractory AML;
Report initial Phase 1 clinical data from RTX-321 for the treatment of HPV 16-positive cancers by the first quarter of 2022; and
Submit an Investigational New Drug Application for RTX-224 by year-end.
Second Quarter Financial Results
Net loss for the second quarter of 2021 was $50.2 million or $0.56 per common share, compared to $37.9 million or $0.47 per common share in the second quarter of 2020.

In the second quarter of 2021, Rubius invested $36.1 million in research and development (R&D) related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $26.1 million in the second quarter of 2020. This year-over-year increase was principally due to a $9.1 million increase in costs incurred for the Company’s lead cancer programs, including, RTX-240 and RTX-321, primarily CRO and internal manufacturing costs incurred in connection with both arms of its Phase 1/2 clinical trial of RTX-240 for the treatment of solid tumors and AML and for its Phase 1 clinical trial of RTX-321 for the treatment of HPV 16-positive cancers. Additionally, personnel-related costs increased $1.2 million for additions to headcount to support the Company’s expanded operations and stock-based compensation expense increased by $1.0 million. Increases in oncology program expenses, personnel-related costs and stock-based compensation expense were offset by a $1.5 million reduction in contract R&D, laboratory supplies and research materials driven primarily by a shift in research activities to support clinical programs.

General and administrative (G&A) expenses were $13.9 million during the second quarter of 2021, as compared to $11.6 million for the second quarter of 2020. The higher costs were driven by a $1.0 million increase in personnel-related costs to support rising headcount in the Company’s general and administrative function, including recruitment costs, as well as a $0.9 million increase in professional and consultant fees and facility-related expenses.

Six Month Financial Results
Net loss for the first six months of 2021 was $92.5 million or $1.08 per common share, compared to $86.3 million or $1.07 per common share in the first six months of 2020.

In the six months ended June 30, 2021, Rubius invested $63.7 million in R&D related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $62.3 million in the first six months of 2020. The year-over-year increase was driven primarily by a $10.9 million increase in costs incurred for the Company’s lead cancer programs. These costs were incurred for its Phase 1/2 clinical trial of RTX-240 for the treatment of solid tumors, including clinical CRO and internal manufacturing costs, as well as costs incurred for its Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers. This increase was partially offset by a $6.7 million reduction in rare disease program costs, following the deprioritization of the Company’s rare disease pipeline in March 2020. Additionally, platform development, early-stage research and other unallocated expenses decreased by $2.8 million due principally to reductions in contract R&D, laboratory supplies and research materials as research activities shifted to support clinical programs.

G&A expenses were $27.1 million during the first six months of 2021, as compared to $24.3 million for the same period in 2020. The higher costs were driven by a $1.0 million increase in personnel-related costs, including recruitment costs, as well as a $1.7 million increase in professional and consultant fees and facility-related expenses.

During the first six months of 2021, other income and expenses decreased by $1.9 million, from other income, net of $0.2 million during the first six months of 2020, to other expense, net of $1.7 million. The change was principally due to lower prevailing interest rates and an increase in outstanding debt following the final borrowing under the Company’s debt facility in June 2020.

Cash Position
As of June 30, 2021, cash, cash equivalents and investments were $298.2 million, compared to $176.3 million as of December 31, 2020. In connection with its underwritten public offering completed in March 2021, the Company received net proceeds of $187.2 million, after deducting underwriting discounts and commission and other offering costs. In addition, during the second quarter, the Company amended its debt facility, postponing principal payments, by two and a half years, until mid-2024.