On May 10, 2021 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported its first-quarter 2021 financial results (Press release, Constellation Pharmaceuticals, MAY 10, 2021, View Source [SID1234579551]). The Company also provided updates on its product candidates pelabresib and CPI-0209.

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"Over the last year, we have advanced the development of pelabresib as a novel therapy for myelofibrosis, and we are pleased to be dosing patients in the Phase 3 MANIFEST-2 trial. Today we are also excited to announce progress on the Phase 2 development plan for our second generation EZH2 inhibitor, CPI-0209. We have determined the recommended Phase 2 dose and the expansion cohorts are open for enrollment, with the first patient dosed. We believe that CPI-0209 provides potential opportunities to treat a wide range of oncology patients," said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. "These are important achievements in moving forward with our goal of becoming a fully integrated hematology / oncology company with a sustainable product pipeline."

Program Updates
pelabresib

Dosing underway in the Phase 3 MANIFEST-2 clinical trial
On May 12, the Company expects the following three abstracts to be published in association with the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting, related to MANIFEST, the ongoing Phase 2 clinical trial of pelabresib:
TITLE: Pelabresib (CPI-0610) improved anemia associated with myelofibrosis: interim results from MANIFEST Phase 2 study (Abstract Code: EP1077)
TITLE: Clinical benefit of pelabresib (CPI-0610) in combination with ruxolitinib in JAK inhibitor treatment naïve myelofibrosis patients: Interim efficacy subgroup analysis from Arm 3 of MANIFEST Phase 2 study (Abstract Code: EP1085)
TITLE: BET inhibitor pelabresib decreases inflammatory cytokines, improves bone marrow fibrosis and function, and demonstrates clinical response irrespective of mutation status in myelofibrosis patients (Abstract Code: EP1080)
CPI-0209

The Company established the recommended Phase 2 dose (RP2D) of CPI-0209 monotherapy as 350 mg once daily. In the Phase 2 expansion cohorts, the Company plans to study CPI-0209 as a monotherapy in patients with cancers such as urothelial, ovarian clear cell and endometrial, where ARID1A mutations are prevalent, and lymphomas, where EZH2 mutations are prevalent. The first patient has been dosed in the expansion cohorts.
On April 10, a poster published in association with the American Association for Cancer Research (AACR) (Free AACR Whitepaper) provided preclinical data suggesting that CPI-0209 has therapeutic potential in androgen receptor-positive prostate cancer.
On May 19, the Company expects the following abstract for a poster to be published in association with the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting related to the Phase 1 portion of the Phase 1/2, clinical trial of CPI-0209:
TITLE: Phase 1/2 first-in-human (FIH) study of CPI-0209, a novel small molecule inhibitor of enhancer of zeste homolog 2 (EZH2) in patients with advanced tumors (Abstract Code: 3104)
Milestones

The Company anticipates achieving the following milestones during 2021:

Pelabresib – Provide MANIFEST translational data update mid-year
Pelabresib – Provide MANIFEST clinical data update and update on new indications by end of year
CPI-0209 – Provide Phase 1 data update by mid-year
CPI-0209 – Provide update on monotherapy cohorts from Phase 2 by end of year
First Quarter 2021 Financial Results

Cash, cash equivalents, and marketable securities as of March 31, 2021, were $382.1 million, a decrease of 9.3% compared to December 31, 2020, primarily due to operating expenses.
Research and development (R&D) expenses increased 53.3% year over year to $30.8 million in the first quarter of 2021, mainly due to increased clinical trial expenses.
General and administrative (G&A) expenses grew 59.8% year over year to $9.4 million in the first quarter of 2021, primarily due to building out the organization of the company.
The net loss attributed to common shareholders increased 57.5% year over year to $40.1 million for the first quarter of 2021, mainly due to increased R&D and G&A expenses. The net loss per share attributable to common shareholders increased 37.7% to $0.84 per share due to an increased net loss, partially offset by an increase in weighted average shares outstanding.
Financial Guidance

Constellation expects that its current cash, cash equivalents, and marketable securities will fund operations into mid-2023.

For further information, please refer to the financial statements filed with the SEC on Form 10-Q, including notes to the financials.

Conference Call

Constellation will host a conference call at 8:00 AM EDT on May 10, 2021, to discuss its clinical programs and financial results. The event will be webcast live and can be accessed on the Investor Relations section of Constellation’s website at View Source To participate in the live question-and-answer session, please dial (877) 473-2077 (domestic) or (661) 378-9662 (international) and refer to conference ID 8798968.

About MANIFEST-2

MANIFEST-2 is a global, blinded, randomized Phase 3 clinical trial with pelabresib in combination with ruxolitinib versus placebo plus ruxolitinib in JAK-inhibitor-naïve patients with primary myelofibrosis or post-ET or post-PV myelofibrosis who have splenomegaly and symptoms requiring therapy. It is designed to enroll approximately 310 patients, randomized 1:1 to the pelabresib + ruxolitinib arm or the placebo + ruxolitinib arm. The primary endpoint of the study is a ≥35% reduction in spleen volume (SVR35) from baseline at 24 weeks. A key secondary endpoint of the study is 50% or greater improvement in Total Symptom Score (TSS50) from baseline at 24 weeks. Other endpoints include bone marrow fibrosis grade improvements, duration of transfusion independence, rate of red-blood-cell transfusion for the first 24 weeks, and hemoglobin response.

About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of pelabresib in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline (SVR35) after 24 weeks of treatment. Constellation is also evaluating CPI-0610, either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy in combination with ruxolitinib in patients with a sub-optimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on TD status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to TI for 12 consecutive weeks. The primary endpoint for the patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment.

About CPI-0209 clinical trial

The Phase 2 portion of the Phase1/2 clinical trial of CPI- 0209 is an open label, single arm study, enrolling up to 29 patients per cohort in the following tumor types: relapsed urothelial carcinoma with known ARID1A mutation; relapsed ovarian clear cell carcinoma with known ARID1A mutation; relapsed endometrial carcinoma with known ARID1A mutation; relapsed or refractory lymphomas of either B-cell or T-cell histology. The goal of these cohorts is to establish the safety and establish the antitumor activity of CPI-0209 as a monotherapy for patients with these tumor types.

On May 10, 2021 Forte Biosciences, Inc. (www.fortebiorx.com) (NASDAQ: FBRX), a clinical-stage biopharmaceutical company reported first quarter 2021 results and provides a general business update on May 10, 2021 (Press release, Tocagen, MAY 10, 2021, View Source [SID1234579578]).

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"Forte has continued to make excellent progress in the fist quarter of 2021. As we have previously highlighted, our randomized clinical trial of FB-401 in atopic dermatitis patients 2 years of age and older, including adolescents and adults, completed enrollment. We expect to report the topline results from that trial in the third quarter of 2021. There is a significant unmet need for safe effective therapies, particularly for children suffering from atopic dermatitis and we are hopeful that FB-401 will address that need," said Paul Wagner, Ph.D., CEO of Forte Biosciences. "In addition to the operational progress, two more patents have now issued, bringing the total number of patents covering FB-401 and our process to eleven as we continue to expand the intellectual property protection."

First Quarter 2021 Results

First Quarter 2021 Business Highlights

In September 2020, Forte initiated a multi-center, placebo-controlled clinical trial of its lead product candidate, FB-401 which was expected to enroll approximately 124 pediatric, adolescent and adult atopic dermatitis subjects aged 2 years of age and older. Enrollment was completed in March 2021 with 154 subjects. Additional information about our Phase 2 trial can be found at ClinicalTrials.gov using the identifier NCT04504279.

Forte ended the first quarter of 2021 with approximately $54.8 million in cash and cash equivalents which Forte believes is sufficient to fund operations for at least the next 12 months. Cash utilization for the first quarter of 2021 was $4.0 million. Forte had approximately 13.5 million shares of common stock outstanding as of March 31, 2021.

First Quarter 2021 Operating Results

Research and development expenses were $3.3 million and $1.4 million for the three months ended March 31, 2021 and 2020, respectively. The increases in 2021 were primarily due to manufacturing, clinical, regulatory and other expenses, including non-cash stock-based compensation, as Forte continues to advance FB-401 through Phase 2 clinical trials.

General and administrative expenses were $1.4 million and $0.7 million for the three months ended March 31, 2021 and 2020, respectively. The increases in 2021 were primarily due to legal, professional, insurance and other expenses as a result of being a public company as well as increases in payroll and related expenses including non-cash stock-based compensation expense as we increased our headcount.

Losses per share were $0.36 and $0.97 for the three months ended March 31, 2021 and 2020, respectively.

Additional detail on our financial results for the first quarter of 2021 can be found in Forte’s Form 10-Q as filed with the SEC on May 10, 2021. You can also find more information in the investor relations section of our website at www.fortebiorx.com.

Conference Call and Webcast Information

Forte management will host a conference call and webcast on Wednesday, May 10th at 4.30 PM Eastern Time. Participants may access the call by dialing 877-705-6003 (Domestic) or 201-493-6725 (International). The conference ID number is: 13719507.

On May 10, 2021 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, reported financial results for the first quarter ending March 31, 2021 and provided a corporate update (Press release, VBI Vaccines, MAY 10, 2021, View Source [SID1234579598]).

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Jeff Baxter, VBI’s President and CEO commented: "The first quarter of 2021 marked the beginning of a transformational year for VBI with notable developments across our lead pipeline programs targeting hepatitis B (HBV), coronaviruses, including different variants of COVID-19, and glioblastoma (GBM). We continue to support the U.S. and European regulatory bodies in their review of our 3-antigen HBV vaccine candidate, and we look forward to ongoing discussions throughout the year. Additionally, our partnerships have enabled us to aggressively advance our pipeline candidates, including the initiation of a first-in-class Phase 2 combination study assessing a potential functional cure regimen for chronic HBV infection as well as a suite of coronavirus vaccine candidates. Most recently, the partnership we entered into with CEPI supports the development of VBI’s enveloped virus-like particle (eVLP) vaccine candidates against known and emerging variants of COVID-19, including B.1.351, the variant first identified in South Africa. With the strength of these partnerships and our financial position, we believe we are well positioned to meet the numerous regulatory and clinical milestones expected over the coming months."

Q1 2021 Key Program Achievements and Anticipated Upcoming Milestones

Hepatitis B (HBV)

3-Antigen HBV Prophylactic Vaccine Candidate

November 30, 2021: U.S. Prescription Drug User Fee Act (PDUFA) target action date set by U.S. Food and Drug Administration (FDA)
European Medicines Agency (EMA) regulatory review ongoing, following acceptance of Marketing Authorization Application (MAA) filing in December 2020
Submissions to United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) and to Health Canada are in process and are expected to be completed this year
VBI-2601 (BRII-179) : HBV Immunotherapeutic

April 2021: Additional data from Phase 1b/2a study in chronic HBV patients demonstrated robust HBV-specific T cell and antibody responses across all study arms
April 2021: Phase 2 combination study of VBI-2601 (BRII-179) and BRII-835 (VIR-2218), Vir Biotechnology’s investigational HBV-targeting siRNA, initiated by partner and trial sponsor, Brii Biosciences (Brii Bio)
2021: Complete Phase 1b/2a study dataset targeted for presentation at scientific conference later this year
COVID-19 & Coronaviruses

March 2021: Announcement of partnership with Coalition for Epidemic Preparedness Innovations (CEPI) – CEPI to provide up to $33 million of funding to support development of VBI’s enveloped virus-like particle (eVLP) vaccine candidates against COVID-19 variants of concern
VBI-2902 : Monovalent COVID-19 Vaccine Candidate

Vaccine candidate supported by funding from the Strategic Innovation Fund of the Government of Canada
March 2021: Adaptive Phase 1/2 clinical study initiated in adults in Canada
Q2 2021: Initial data from ongoing Phase 1/2 study expected by the end of the second quarter
VBI-2905 : Monovalent COVID-19 (B.1.351 Variant) Vaccine Candidate

Vaccine candidate supported by funding from CEPI
Mid-year 2021: Phase 1 clinical study expected to initiate
VBI-2901 : Multivalent Pan-Coronavirus Vaccine Candidate

Vaccine candidate supported by funding from the Strategic Innovation Fund of the Government of Canada
H2 2021: Phase 1 clinical study expected to initiate
Glioblastoma (GBM)

VBI-1901: Cancer Vaccine Immunotherapeutic Candidate

Q2 2021: Additional data, including tumor response and 6-month and 12-month overall survival data from Phase 2a (Part B) of ongoing Phase 1/2a study expected
Q4 2021: Expected initiation of a randomized, controlled clinical study with the potential to yield registrational data
Financing

Throughout the first quarter of 2021, VBI raised total gross proceeds of $22.1 million, issuing 5.8 million shares at an average price of $3.84 through its Open Market Sales AgreementSM, established July 31, 2020 with Jefferies LLC
First Quarter 2021 Financial Results

Cash Position: VBI ended the first quarter of 2021 with $133.6 million in cash, cash equivalents, and short-term investments compared with $119.1 million as of December 31, 2020.
Net Cash Used in Operating Activities: Net cash used in operating activities for the three months ended March 31, 2021 was $6.6 million, compared to $7.6 million for the same period in 2020. The decrease is largely a result of the change in operating working capital, notably the cash received in advance from the CEPI funding agreement, offset by an increase in net loss.
Cash Used for Purchase of Property and Equipment: Cash used for the purchase of property and equipment was $0.6 million for the three months ended March 31, 2021, compared to $0.1 million for the same period in 2020. The increase is a result of routine purchases of property and equipment.
Revenue: Revenue in the first quarter of 2021 was $0.3 million, compared to $0.4 million for the same period in 2020. The decrease in revenues was due to a decrease in R&D services revenue as part of the collaboration with Brii Bio. Fewer manufacturing and non-clinical research services were required in the three months ended March 31, 2021 compared to the three months ended March 31, 2020.
Cost of Revenues: Cost of revenues was $2.4 million in the first quarter of 2021 as compared to $2.6 million for the same period in 2020. The decrease in the cost of revenues was due to the decrease in VBI-2601 R&D services referenced above.
Research and Development (R&D): R&D expenses for the first quarter of 2021 were $6.8 million compared to $3.2 million in the first quarter of 2020. The increase was a result of increased expenses related to our coronavirus vaccine program, which was offset by a decrease in the R&D expenses related to the 3-antigen prophylactic HBV vaccine candidate, the final Phase 3 clinical study of which (CONSTANT) completed in January 2020, and regulatory costs related to the BLA submission for the 3-antigen prophylactic HBV vaccine candidate.
General and Administrative (G&A): G&A expenses were $6.7 million for the first quarter of 2021, compared to $4.1 million for the same period in 2020. The increase was a result of the increased pre-commercialization activities related to the 3-antigen prophylactic HBV vaccine candidate in preparation for potential regulatory approvals, in addition to increased insurance and labor costs.
Net Loss: Net Loss and net loss per share for the first quarter of 2021 were $17.6 million and $0.07, respectively, compared to a net loss of $8.4 million and a net loss per share of $0.05 for the first quarter of 2020.

On May 10, 2021 Hologic, Inc. (Nasdaq: HOLX) reported that its subsidiary, Biotheranostics, Inc., has received broader Medicare coverage for its Breast Cancer Index test under an expanded Medicare Local Coverage Determination (LCD: L37822) effective today (Press release, Hologic, MAY 10, 2021, View Source [SID1234579617]).

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Under the new criteria, the Breast Cancer Index test is now covered for post-menopausal women diagnosed with early-stage node-positive (one to three axillary lymph nodes), non-relapsed, estrogen receptor (ER) and/or progesterone receptor (PR) positive, HER2 negative breast cancer to help physicians manage treatment of the patient. Previously, Medicare covered the test only for patients with node-negative, non-relapsed, ER and/or PR positive, HER2 negative breast cancer. Therefore, the expanded coverage increases the availability of Breast Cancer Index testing with no cost to Medicare beneficiaries who meet the LCD criteria.

"Expansion of Medicare coverage for the Breast Cancer Index test and its recent inclusion in National Comprehensive Cancer Network guidelines are major milestones toward making the test standard of care for all early-stage, HR+ breast cancer patients," said Kevin Thornal, division president, Diagnostic Solutions at Hologic.

For hormone receptor positive (HR+) post-menopausal breast cancer patients on extended endocrine therapy, the side effects and toxicities of treatment often have significant negative effects on health and quality of life, such as osteoporosis, bone fractures and joint pain. As a result, knowing when extended endocrine therapy will benefit a patient is as important as avoiding it when it will not make a difference. The Breast Cancer Index test can help personalize extended endocrine treatment for all HR+ early-stage patients.

The ratio of breast cancers diagnosed as node-negative or node-positive varies year to year, but according to data published by the National Cancer Institute1 in 2021, approximately 85% of early-stage, HR+ breast cancers were node-negative and 15% were node-positive that year. This means that approximately 25,000 more women every year will be eligible for testing with Breast Cancer Index based on the expanded coverage.

About Breast Cancer Index

Breast Cancer Index is a molecular, gene expression-based test uniquely positioned to provide information to help physicians individualize treatment decisions for patients with early-stage, HR+ breast cancer. This breakthrough test helps oncologists and patients navigate the difficult trade-offs between taking steps to prevent recurrence of their disease and facing significant side effects and safety challenges related to unnecessary treatment. Breast Cancer Index has guideline designation from the American Joint Committee on Cancer for cancer staging based on molecular profile. ASCO (Free ASCO Whitepaper), NCCN, the European Group on Tumor Markers (EGTM) and St. Gallen acknowledge Breast Cancer Index as a biomarker to inform the chemotherapy decision; ASCO (Free ASCO Whitepaper), NCCN and EGTM to inform the extended endocrine treatment decision. It is the only validated, commercially available test that predicts benefit from extended endocrine therapy. Breast Cancer Index is intended for routine clinical use, and treatment decisions based on results are the responsibility of the physician. It is a laboratory developed test (LDT) performed in a CLIA-certified and CAP-accredited diagnostic laboratory and is not required to be cleared or approved by the US Food and Drug administration. For more information, visit www.breastcancerindex.com.

On May 10, 2021 Race Oncology Limited ("Race") reported a team of researchers, led by Professor Borje Andersson and Associate Professor Ben Valdez of the MD Anderson Cancer Center (Texas, USA), have identified a number of clinically translatable drug combinations that showed synergy with Bisantrene when tested in Acute Myeloid Leukaemia (AML) cells (Press release, Race Oncology, MAY 10, 2021, View Source [SID1234580138]).

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This study1, sponsored by Race, has been published in the Journal of Clinical & Experimental Oncology and is entitled "Synergism of the Anthracene-Derivative Anti-Cancer Agent Bisantrene with Nucleoside Analogs and A Bcl-2 Inhibitor in Acute Myeloid Leukemia Cells".

The MD Anderson team identified that Bisantrene, when used in combination with the standard-of-care AML drugs cytarabine, cladribine, fludarabine, clofarabine and/or ABT199 (Venetoclax) showed enhanced activation of apoptosis (cell killing) in AML cells. Combinations of three or more of these drugs with Bisantrene showed additional synergism and effective cell killing at drug concentrations far below that observed when the drugs were used on their own.

This work provides the preclinical data to support our upcoming Phase II relapsed / refractory AML trial at the Chaim Sheba Medical Center, where patients will be treated with Bisantrene in combination with the nucleoside analogs, clofarabine and fludarabine. This trial is scheduled to begin in Q2 CY2021. We are extremely excited about being able to quickly translate this work from the lab into the clinic, where it has the potential to help AML patients in need.