On January 25, 2022 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage biopharmaceutical company dedicated to delivering targeted therapies for rare cancers, reported positive topline data from the pivotal Phase 3 MOMENTUM study—a global, randomized, double-blind clinical trial evaluating momelotinib (MMB) in myelofibrosis patients who are symptomatic and anemic and previously treated with an approved JAK inhibitor (Press release, Sierra Oncology, JAN 25, 2022, View Source [SID1234606769]). The trial met all of its primary and key secondary endpoints.

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"These data are extremely exciting and everything we had hoped to see from the trial," said Stephen Dilly, MBBS, PhD, President and Chief Executive Officer of Sierra Oncology. "To achieve statistically significant and clinically important efficacy across all prespecified primary and key secondary endpoints while maintaining platelet counts in such a difficult to treat patient population is remarkable, and a confirmation of the anemia response we identified in the comprehensive review of our previous Phase 3 studies."

Topline data announced based on 195 patients (MMB n = 130; DAN n = 65) include:

Primary Endpoint of Total Symptom Score (TSS) of >50%: 25% in the MMB arm vs. 9% in the control arm (p=0.0095)
Secondary Endpoint of Transfusion Independence (TI): 31% in the MMB arm vs. 20% in the control arm (one-sided p=0.0064; non-inferiority)
Secondary Endpoint of Splenic Response Rate (SRR) >35%: 23% in the MMB arm vs. 3% in the control arm (p=0.0006)
The rate of Grade 3 or worse adverse events in the randomized treatment period was 54% in the MMB arm and 65% in the control arm. Serious treatment emergent adverse events were 35% in the MMB arm and 40% in the control arm.
Mean baseline characteristics for all patients were TSS of 27, Hemoglobin (Hgb) of 8 g/dL and platelet count of 145 x 10 9/L
The full data set will be presented at an upcoming medical meeting
"As a clinician, I am thrilled to see data that confirm the potential of momelotinib as a treatment option for myelofibrosis patients who are anemic or at risk of becoming anemic," said Ruben Mesa, MD, FACP, Executive Director of the Mays Cancer Center, home to UT Health San Antonio, MD Anderson Cancer Center, and co-Principal Investigator of the study. "Anemia of myelofibrosis is strongly correlated with reduced quality of life and a decrease in overall survival. Half of all myelofibrosis patients present with anemia at diagnosis and virtually all become anemic over time. With currently approved therapies being myelosuppressive, it’s wonderful to know that we may soon have such an effective treatment option for these patients."

Barbara Klencke, MD, Chief Medical Officer of Sierra Oncology, stated, "We are committed to working tirelessly to bring momelotinib to patients as quickly as possible. We would like to thank the patients and investigators who participated in this study and look forward to presenting the full data set at an upcoming medical meeting."

Conference Call & Webcast
In connection with this announcement, Sierra will host a conference call and webcast on Tuesday, January 25, 2022, at 8:00 am ET. The call may be accessed by calling (833) 927-1758 (Toll-free in North America) or +1 (929) 526-1599 (International Dial-in) and entering the Conference ID number: 007608. The call will be webcast live and will be accessible through the Investor section of the Company’s website at www.SierraOncology.com. An archived replay of the webcast will be made available at the same location.

About Momelotinib
Momelotinib is a potent, selective and orally bioavailable JAK1, JAK2 and ACVR1 / ALK2 inhibitor under investigation for the treatment of myelofibrosis in symptomatic, anemic patients previously treated with an approved JAK inhibitor. More than 1,200 subjects have received momelotinib since clinical studies began in 2009, including approximately 1,000 patients treated for myelofibrosis, several of whom remain on treatment for over 11 years. Momelotinib is the first and only JAK inhibitor to demonstrate positive data for all key hallmarks of the disease—symptoms, splenic response and anemia.

About Myelofibrosis
Myelofibrosis is a rare blood cancer that results from dysregulated JAK-STAT signaling and is characterized by constitutional symptoms, splenomegaly (enlarged spleen) and progressive anemia. From prior studies with momelotinib, we know approximately half of myelofibrosis patients are moderately to severely anemic when eligible for JAK inhibitor treatment. Furthermore, currently approved JAK inhibitors only address symptoms and splenomegaly and are myelosuppressive. This can lead to worsening anemia, resulting in dose reductions that potentially reduce treatment effect.

About the Pivotal MOMENTUM Clinical Trial
MOMENTUM is a global, randomized, double-blind Phase 3 clinical trial of momelotinib versus danazol in patients with myelofibrosis who were symptomatic and anemic, and had been previously treated with an FDA-approved JAK inhibitor. The study was designed to evaluate the safety and efficacy of momelotinib for the treatment and reduction of the key hallmarks of disease: symptoms, blood transfusions (due to anemia) and splenomegaly (enlarged spleen).

The primary endpoint of the study is Total Symptom Score (TSS) reduction of >50% over the 28 days immediately prior to the end of Week 24 compared to baseline TSS, using the Myelofibrosis Symptom Assessment Form (MFSAF). Secondary endpoints included Transfusion Independence (TI) rate for >12 weeks immediately prior to the end of Week 24 with Hgb levels ≥ 8 g/dL, and Splenic Response Rate (SRR) based on splenic volume reduction of >35% at Week 24. The study enrolled 195 patients based on a planned 180 patients across 21 countries.

Danazol was selected as the treatment comparator given its use to ameliorate anemia in patients with myelofibrosis, as recommended by National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) guidelines. Patients were randomized 2:1 (MMB n = 130 and DAN n = 65) to receive either momelotinib or danazol. After 24 weeks of treatment, patients on danazol were allowed to crossover to receive momelotinib. Early cross-over to momelotinib was available for confirmed symptomatic splenic progression.

On January 25, 2022 Checkpoint Therapeutics, Inc. ("Checkpoint") (NASDAQ: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported positive topline results from its registration-enabling clinical trial evaluating the safety and efficacy of its anti-PD-L1 antibody, cosibelimab, administered as a fixed dose of 800 mg every two weeks in patients with metastatic cutaneous squamous cell carcinoma ("cSCC") (Press release, Checkpoint Therapeutics, JAN 25, 2022, View Source [SID1234606768]).

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The study met its primary endpoint, with cosibelimab demonstrating a confirmed objective response rate ("ORR") of 47.4% (95% CI: 36.0, 59.1) based on independent central review of 78 patients enrolled in the metastatic cSCC cohort using Response Evaluation Criteria in Solid Tumors version 1.1 ("RECIST 1.1") criteria. The median duration of response ("DOR") had not yet been reached at the data cut-off point (76% of responses are ongoing). Safety data across 201 patients with advanced cancers enrolled and treated in all cohorts of the ongoing study remain consistent with those previously reported, with the majority of treatment-emergent adverse events reported as Grade 1 or 2 in severity. Based on these results, Checkpoint intends to submit a Biologics License Application ("BLA") to the U.S. Food and Drug Administration for cosibelimab later this year, to be followed by a marketing authorization application ("MAA") submission in Europe and additional potential submissions in markets worldwide.

"Most people don’t realize that cutaneous squamous cell carcinoma is the second most common form of skin cancer. While treatable with surgery when caught early, cSCC patients diagnosed with advanced disease that has recurred or metastasized have traditionally faced a poor prognosis and often suffer from painful physical discomfort," commented Professor Philip Clingan, Medical Oncologist at Southern Medical Day Care Centre in Australia and co-principal investigator of the trial. "These impressive results demonstrate that cosibelimab, a novel PD-L1 antibody with a unique two-fold mechanism of action, has the potential to offer physicians a new treatment option that provides compelling efficacy, complemented by a favorable tolerability profile, for patients living with this devastating disease."

James F. Oliviero, President and Chief Executive Officer of Checkpoint, stated, "We are thrilled to report these topline results from our pivotal trial of cosibelimab in metastatic cutaneous squamous cell carcinoma. We believe the strong ORR result is attributable to cosibelimab’s differentiated, two-fold mechanism of action of engaging both T-cells and natural killer cells, while also demonstrating a potential favorable safety profile through its binding to PD-L1, reported in literature as associated with lower rates of severe or worse adverse events as compared to PD-1 therapy. We extend our sincere thanks to the patients, caregivers, investigators and their site staff for their dedication to this trial, particularly during these challenging times globally. We look forward to a detailed presentation of the data at an upcoming medical meeting."

Mr. Oliviero continued, "Upon approval, we intend to position cosibelimab at a lower price point than currently available PD-(L)1 therapies, which we hope will lead to meaningful market share in the U.S. and international markets around the world. We also believe the safety and efficacy profile of cosibelimab could make cosibelimab an attractive agent for use in combination regimens, potentially with drug candidates within our current portfolio, additional molecules we may in-license, and synergistic molecules through potential collaborations, particularly those that can take advantage of the two-fold mechanism of action of cosibelimab."

Additionally, Checkpoint continues to enroll a registration-enabling cohort of patients with locally advanced cSCC, anticipating this potential second indication could be included in the planned initial BLA submission, as well as the global, randomized Phase 3 (CONTERNO) trial of cosibelimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with non-squamous non-small cell lung cancer.

Conference Call Information

Checkpoint will host a conference call today, Tuesday, January 25, 2022, at 8:30 AM ET to discuss the topline results. In order to participate in the conference call, please dial 1-877-269-7756 (U.S.), 1-201-689-7817 (outside of the U.S.).

A live webcast of this conference call will be available on the IR Calendar page under News & Events, located within the Investors section of Checkpoint’s website, View Source, and an audio recording of the conference call will also be available for replay for a period of approximately 30 days following the call.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately 1 million cases according to the Skin Cancer Foundation. While most cases are localized tumors amenable to curative resection, approximately 40,000 cases will become advanced and an estimated 15,000 people will die from their disease. In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear.

About Cosibelimab

Cosibelimab (formerly referred to as CK-301) is a potential best-in-class, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 ("PD-L1") and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained >99% target tumor occupancy to reactivate an antitumor immune response and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity ("ADCC") for potential enhanced efficacy in certain tumor types.

On January 25, 2022 Cartesian Therapeutics, a fully integrated clinical-stage biotechnology company pioneering RNA cell therapy in and beyond oncology, reported that it has dosed the first patient in a Phase 1/2a multicenter clinical study evaluating Descartes-25 in patients with multiple myeloma (Press release, Cartesian Therapeutics, JAN 25, 2022, View Source [SID1234606767]). To the company’s knowledge, Descartes-25 is the first off-the-shelf RNA cell therapy to enter clinical trials for any cancer and marks the company’s fifth FDA Investigational New Drug (IND) allowance in five years. Descartes-25 is produced at Cartesian’s wholly owned cGMP manufacturing facility with the company’s proprietary RNA Armory cell manufacturing platform. This platform now includes an internally developed, Part 1271-compliant Master Cell Bank of human umbilical cord Mesenchymal Stem Cells (MSC) that was used to engineer Descartes-25.

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Descartes-25 is designed to deliver two complementary antitumor proteins directly to the tumor: a novel three-arm bispecific antibody that binds B-cell Maturation Antigen (BCMA) with femtomolar avidity and the potent antitumor cytokine interleukin-12 (IL-12). Descartes-25 cells are further engineered with a membrane-bound homing protein that directs the cells to the tumor microenvironment for local delivery of their antitumor cargo. In preclinical models, Descartes-25’s IL-12 synergistically potentiates its BCMA bispecific antibody to eliminate myeloma with unprecedented activity.

"Patients with relapsed and/or refractory multiple myeloma have few treatment options remaining," said Kenneth Anderson, M.D., Kraft Family Professor of Medicine at Harvard Medical School and Director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics. "A cell therapy that locally delivers a combination of a BCMA-bispecific antibody and IL-12, without using lymphodepleting chemotherapy, is an elegant and highly innovative approach. If approved, it will be a welcome addition to our toolkit for treating this currently incurable disease."

"We designed Descartes-25 to be highly potent and well tolerated by focusing on creating the ideal pharmacokinetic profile: continuous, measured, and local delivery of a synergistic combination of antitumor agents," said Murat Kalayoglu, M.D., Ph.D., President and Chief Executive Officer at Cartesian. "I am proud of our integrated team of scientists and physicians for their hard work and rapid clinical translation of this first-in-class therapy."

"With Descartes-25, Cartesian scientists used RNA Armory technology to convert stem cells into a targeted combination therapy," said Chief Scientific Officer Michael Singer, M.D., Ph.D. "Therefore Descartes-25 is not just a potent antitumor therapy. It’s also a blueprint for future RNA cell therapies to deliver three or more rationally selected and spatially targeted combination therapeutics for a diverse array of diseases."

About the Phase 1/2a Clinical Trial

The Phase 1/2a study (NCT05113342) is an open-label, multicenter, dose escalation trial for Descartes 25 in patients with relapsed and/or refractory multiple myeloma. The study aims to enroll twenty patients who have previously failed two or more lines of treatment to determine the safety and preliminary efficacy of Descartes-25. For more information visit View Source

About RNA Armory

The RNA Armory is Cartesian’s proprietary cell engineering platform that generates large-scale, potent RNA cell therapies with extended protein expression. The RNA Armory is currently focused on RNA engineering two types of cells, T-cells and Mesenchymal Stem Cells (MSCs). Our CAR T-cell programs harness the safety of RNA and autologous engineering to target autoimmune diseases and frontline cancer – without lymphodepletion. Our off-the-shelf MSC programs leverage these cells’ clinical safety record and excellent capacity for protein secretion to deliver synergistic combinations of therapies. For more information visit View Source

On January 25, 2022, Bolt Biotherapeutics, Inc. (the "Company") reported that entered into an amended and restated supply agreement with EirGenix, Inc. (the "Amended Supply Agreement"), which amends the original supply agreement with EirGenix, Inc. ("EirGenix") dated March 10, 2019, pursuant to which EirGenix agreed to supply to the Company, on a non-exclusive basis, bulk drug substance of EG12014, its monoclonal antibody being developed as a biosimilar of trastuzumab, which the Company uses in the manufacture of its BDC-1001 HER2 Boltbody ISAC (Filing, 8-K, Bolt Biotherapeutics, JAN 25, 2022, View Source [SID1234606766]). The Amended Supply Agreement, among other things, requires the constitution of a joint steering committee, amends the forecasting schedules and methods of addressing any order delays or cancellations, and adjusts supply pricing based on the scale of production. The remaining terms and conditions under the Amended Supply Agreement remained substantially the same as the original supply agreement.

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Under the Amended Supply Agreement, EirGenix provides the Company with its regulatory data package containing the sections of chemistry, manufacturing and control of drug substance EG12014 to facilitate the Company’s development and commercialization efforts, and the Company is required to make milestone payments to EirGenix up to an aggregate of $2.0 million based upon achievement of certain regulatory milestones by the Company’s HER2 Boltbody ISAC. The agreement will remain in effect as long as the Company, or any of its affiliates or licensees, continue to pursue the development or commercialization of any Boltbody ISAC containing drug substance EG12014, unless earlier terminated in accordance with the terms of the Amended Supply Agreement.

On January 25, 2022 Biomea Fusion, Inc. ("Biomea") (Nasdaq: BMEA), reported that the first patient has been dosed in its Phase I clinical trial evaluating BMF-219, the company’s irreversible covalent menin inhibitor, in patients with relapsed/refractory (r/r) acute leukemias, including those with MLL1/KMT2A gene rearrangements or NPM1 mutations (Press release, Biomea Fusion, JAN 25, 2022, View Source [SID1234606765]).

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"We are honored and deeply humbled by this significant milestone, which marks our successful transition to a clinical stage company. Just over four years ago, we took the concept of designing a small molecule that targets menin and brought forward BMF-219 to the clinic to significantly improve the lives of patients," said Thomas Butler, Biomea’s Chief Executive Officer and Chairman of the Board. "I’m incredibly proud of our team for their ability to execute on this aggressive timeline. This signals how we intend to operate as a drug discovery and development organization – advancing world-class science with rapid momentum and driven by an unwavering mission to improve patient outcomes and save lives. We are pursuing a novel approach to developing best-in-class molecules with our FUSION System across multiple indications and anticipate announcing our next pipeline candidate in the first half of 2022."

"Since 2017, we have focused on building a world-class discovery and development team at Biomea Fusion. We have internally developed our FUSION System, which allows us to expeditiously target validated cancer biology with breakthrough covalent chemistry. Our pipeline assets are designed to achieve higher selectivity, deeper target inactivation and thereby afford patients a greater therapeutic window. BMF-219 is just our first asset graduating now into clinical development. Our team has evolved significantly and is set up today not only to explore the full potential of BMF-219 and the inhibition of the menin pathway but also to advance several other programs into the clinic," said Ramses Erdtmann, President of Biomea Fusion. "We are an integrated biotech company engaged in all phases of drug discovery and clinical development. We have come a long way and are now set up to fully explore pre-clinically and clinically innovative therapies for the benefit of patients."

The current Phase I, open-label, multi-center, dose escalation and dose expansion study is designed to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics of once daily oral dosing of BMF-219 in patients with r/r acute leukemias, including subpopulations where menin inhibition is expected to provide a therapeutic benefit (e.g., patients with MLL1/KMT2A gene rearrangements or NPM1 mutations). Additional information about the Phase I trial of BMF-219 can be found at ClinicalTrials.gov using the identifier NCT05153330.

Acute Myeloid Leukemia (AML) and Acute Lymphocytic Leukemia (ALL)

AML is the most common form of acute leukemia in adults and is responsible for the largest number of annual leukemia deaths in the U.S. and Europe. AML originates within the white blood cells in the bone marrow and can rapidly move to the blood and other parts of the body, including the lymph nodes, spleen, and central nervous system. Approximately 20,000 people in the U.S. are diagnosed with AML each year, and the five-year overall survival rate in adults is roughly 29% (Source: NCI SEER Data). Among patients with relapsed/refractory disease, the need is greatest, as the overall survival is approximately 3 to 9 months. It is estimated that upwards of 45% of AML patients have menin dependent genetic drivers (e.g., MLL1/KMT2A gene rearrangements or NPM1 mutations). ALL is a less common leukemia, with approximately 6,000 new cases in the U.S. each year and a higher five-year survival rate of nearly 70% (Source: NCI SEER Data). Between 10-15% of adult ALL patients and 60-70% of pediatric ALL patients have MLL1/KMT2A gene rearrangements.