On December 11, 2020 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported the opening for patient screening and enrollment of the IMpactMF Phase 3 clinical trial of imetelstat, a first-in-class telomerase inhibitor, in refractory myelofibrosis (MF) (Press release, Geron, DEC 11, 2020, View Source [SID1234572658]).

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"As Geron’s second registration-enabling Phase 3 trial in hematologic myeloid malignancies, the IMpactMF trial represents a milestone for our Company," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "The IMpactMF trial will evaluate imetelstat in a poor-prognosis refractory MF patient population to confirm the clinical benefits of extended overall survival and symptom improvement observed in our IMbark Phase 2 trial, as well as the reductions in abnormal clones and mutation burden demonstrating disease-modifying activity of imetelstat."

Geron plans for IMpactMF to evaluate imetelstat compared to best available therapy (BAT) in approximately 320 patients with Intermediate-2 or High-risk MF. Patients eligible for the trial will be required to be non-responsive, or refractory, to treatment with a JAK inhibitor. The primary efficacy endpoint for the Phase 3 trial is overall survival (OS). Secondary endpoints include symptom response, spleen response, progression free survival, duration of response, safety, pharmacokinetics and patient reported outcomes. Geron plans to engage over 150 sites to participate in IMpactMF across North America, South America, Europe and Asia, with the majority of clinical sites expected to be open for screening and enrollment in 2021, subject to potential delays or interruptions associated with the evolving and uncertain effects of the COVID-19 pandemic.

To learn more about IMpactMF and whether the study is enrolling patients in your area, please visit www.clinicaltrials.gov.

About Myelofibrosis (MF)

Myelofibrosis, a type of myeloproliferative neoplasm, is a chronic blood cancer in which abnormal or malignant precursor cells in the bone marrow proliferate rapidly, causing scar tissue, or fibrosis, to form. People with MF may have abnormally low or high numbers of circulating red blood cells, white blood cells or platelets, and abnormally high numbers of immature cells in the blood or bone marrow. MF patients can also suffer from debilitating constitutional symptoms, such as drenching night sweats, fatigue, severe itching, or pruritus, abdominal pain, fever and bone pain.

Approximately 70% of MF patients are classified as having Intermediate-2 or High-risk disease, as defined by the Dynamic International Prognostic Scoring System Plus. There are more than 35,000 patients worldwide and more than 13,000 patients in the U.S. living with Intermediate-2 or High-risk MF. The only drug therapies approved for treating these MF patients are JAK inhibitors. Currently, MF patients who fail or no longer respond to JAK inhibitor treatment have no or limited options, resulting in shortened median overall survival.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Phase 2 clinical data strongly suggest that imetelstat has disease-modifying activity through the apoptosis of malignant stem and progenitor cells, which allows potential recovery of normal hematopoiesis. Geron is currently conducting two registration-enabling Phase 3 clinical trials of imetelstat: IMerge, a Phase 2/3 trial in lower risk myelodysplastic syndromes (MDS), and IMpactMF, a Phase 3 trial in refractory myelofibrosis (MF). Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.

On December 11, 2020 Bristol Myers Squibb (NYSE: BMY) reported that its wholly owned subsidiary, Celgene, and Cipla Limited (Cipla) have settled their litigation related to patents for REVLIMID (lenalidomide) (Press release, Bristol-Myers Squibb, DEC 11, 2020, View Source [SID1234572692]).

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As part of the settlement, the parties will file Consent Judgments with the United States District Court for the District of New Jersey that enjoin Cipla from marketing generic lenalidomide before the expiration of the patents-in-suit, except as provided for in the settlement, as described below.

In settlement of all outstanding claims in the litigation, Celgene has agreed to provide Cipla with a license to Celgene’s patents required to manufacture and sell certain volume-limited amounts of generic lenalidomide in the United States beginning on a confidential date that is some time after March 2022. For each consecutive twelve-month period (or part thereof), following the volume-limited entry date until January 31, 2026, the volume of generic lenalidomide sold by Cipla cannot exceed certain agreed-upon percentages. The specific volume-limited license date and percentages are confidential. In addition, Celgene has agreed to provide Cipla with a license to Celgene’s patents required to manufacture and sell an unlimited quantity of generic lenalidomide in the United States beginning no earlier than January 31, 2026.

Cipla’s ability to market lenalidomide in the U.S. will be contingent on its obtaining approval of an Abbreviated New Drug Application.

On December 11, 2020 Exact Sciences Corp. (NASDAQ: EXAS) reported the presentation of new data at the virtual 2020 San Antonio Breast Cancer Symposium (SABCS) building on the clinical value of the Oncotype DX Breast Recurrence Score test (Press release, Exact Sciences, DEC 11, 2020, View Source [SID1234572659]). These data highlight the role of the test in further individualizing treatment decisions in early breast cancer.

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"These latest presentations, including data from the RxPONDER trial, further highlight the unique value of the Recurrence Score result in providing critical information to personalize and improve the quality of treatment decisions in node-negative and node-positive early breast cancer," said Rick Baehner, MD, chief medical officer of Precision Oncology at Exact Sciences.

Five-year outcomes from ADAPT study show that not all clinically high-risk patients with node-negative or node-positive disease need chemotherapy

First efficacy results from the ADAPT study (4,691 patients) were presented at SABCS.[i]Patients were all considered candidates for chemotherapy by traditional parameters and were stratified using the Oncotype DX test and changes in the immunohistochemical prognostic marker Ki67 after three weeks of pre-operative anti-hormonal therapy. Patients with clinically high risk node-negative disease, and node-positive disease with up to 3 positive nodes, were treated with anti-hormonal therapy alone if the Recurrence Score result was 0–11 or if the Recurrence Score result was 12-25 with a Ki67 response. This group of patients had, regardless of their age, favorable outcomes with anti-hormonal therapy alone, with 5-year distant disease-free survival of 96%.

Another analysis from the ADAPT trial also presented at SABCS evaluated 864 breast cancer patients who received neoadjuvant chemotherapy primarily based on their Recurrence Score result.[ii] These results from a large neoadjuvant trial showed that the Recurrence Score result is a strong predictor of response to chemotherapy as assessed by the rate of pathologic complete response (no residual invasive tumor).

ADAPT is one of the largest prospective, randomized studies in early-stage breast cancer and was conducted by the West German Study Group (WSG) in 80 centers across Germany. It utilized a pioneering trial design to assess individualization of (neo)adjuvant decision-making.

"Our study shows the unique value of the complementary biological information provided by the Oncotype DX test and sequential Ki67 testing. Risk stratification using the Recurrence Score result and changes in Ki67 after brief pre-operative anti-hormonal therapy allows us to identify those patients with node-negative or node-positive disease who can be spared the toxicity and side effects of chemotherapy without a negative impact on treatment outcome," said Prof. Nadia Harbeck, Scientific Director of the WSG and Head of the Breast Centre at LMU Klinikum Munich (LMU), Germany. "This is especially important for patients who would be considered at high risk of relapse based on traditional clinical parameters."

New patient-specific meta-analysis provides individualized estimates for both prognosis and absolute chemotherapy benefit in node-negative breast cancer

A new patient-specific meta-analysis of data from more than 10,000 patients with node-negative disease assessed individualized estimates of distant recurrence risk and absolute chemotherapy benefit based on the integration of the Recurrence Score result with clinicopathologic features.[iii]This analysis builds on the practice-changing results from the TAILORx study, which prospectively defined the groups of patients who will and will not benefit from chemotherapy.

The meta-analysis was conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and was presented in an oral session at SABCS by lead author Joseph A. Sparano, M.D., associate director for clinical research at Albert Einstein Cancer Center and associate chair for clinical research in the department of oncology at Montefiore Health System in New York, and leader of the TAILORx study for the ECOG-ACRIN Cancer Research Group. The data was published concurrently in the December 2020 issue of the Journal of Clinical Oncology.

The patient-specific meta-analysis estimates will initially be made available to physicians in the United States, starting in December 2020, as an online educational tool called RSClin. The tool provides a more individualized prediction of absolute chemotherapy benefit that can enhance treatment decisions, particularly for patients whose Recurrence Score result is close to the TAILORx defined cut-off point of 25. By presenting the data in a new, easy-to-understand, visual format, RSClin empowers physicians with information that may be used to facilitate treatment conversations and decision-making with patients.

"As confirmed in TAILORx, for the great majority of patients, treatment based on the Recurrence Score result alone is clear," said Dr. Sparano. "The RSClin tool, which now incorporates data from TAILORx to reflect contemporary treatment outcomes, provides individualized estimates for both risk of distant recurrence and absolute chemotherapy benefit and continues to demonstrate the role of TAILORx in informing early-stage breast cancer treatment."

ECOG-ACRIN conducted the analysis primarily with funding from the National Cancer Institute. Mention of commercial products does not imply endorsement by the U.S. government. Additional support was provided by the Breast Cancer Research Foundation, the Komen Foundation, and the Breast Cancer Research Stamp issued by the United States Postal Service.

On December 11, 2020 PureTech Health plc (LSE: PRTC, Nasdaq: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported the initiation of its Phase 1 clinical trial of LYT-200 for the potential treatment of metastatic solid tumors that are difficult to treat and have poor survival rates (Press release, PureTech Health, DEC 11, 2020, View Source [SID1234572693]). LYT-200 is one of several novel therapeutic opportunities within PureTech’s Wholly Owned Pipeline that will be discussed today at its virtual R&D Day.

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"Each year, hundreds of thousands of people are diagnosed with solid tumors, and many will present with metastatic disease that do not respond to existing immunotherapy agents," said Zev Wainberg, M.D., co-director of the UCLA GI Oncology Program, associate professor of medicine at UCLA and the principal investigator on PureTech’s LYT-200 trial. "By targeting galectin-9, LYT-200 is designed to block foundational immunosuppressive mechanisms that shut down the body’s natural ability to fight a number of cancers. The unique mechanism of LYT-200 holds potential across a number of solid tumor types and may enable LYT-200 to be used as a single agent, as well as in combination with checkpoint inhibitors and other anti-cancer treatments."

LYT-200 is a clinical stage, fully human, monoclonal antibody (mAb), that is designed to target galectin-9, an immunosuppressive protein that simultaneously activates multiple immunosuppressive pathways in the tumor microenvironment and is prominently expressed in multiple difficult-to-treat cancers, including breast cancer, pancreatic and cholangiocarcinoma. It is currently being evaluated in the first stage of an adaptive Phase 1/2 trial. The primary objective of the Phase 1 portion of the trial is to assess the safety and tolerability of escalating doses of LYT-200 in order to identify a dose to carry forward into a subsequent Phase 2 trial. The Phase 1 will also assess LYT-200’s pharmacokinetic and pharmacodynamic profiles. Following the topline results, which are expected in the fourth quarter of 2021, PureTech intends to initiate the Phase 2 expansion cohort portion of the trial, which will further assess the recommended Phase 2 dose as a single agent or in combination with chemotherapy and anti-PD-1 therapy in multiple solid tumor types, including pancreatic cancer and cholangiocarcinoma.

"We are pleased to have initiated the Phase 1 part of our LYT-200 clinical trial, which is a dose-finding portion designed to assess safety and tolerability and explore preliminary signals of efficacy for LYT-200," said Aleksandra Filipovic, M.D. PhD, head of oncology at PureTech. "We have generated compelling preclinical data to date, which we believe support the potential of LYT-200 as a new anti-cancer therapy targeting galectin-9, both as a single agent and in combination with other anti-cancer therapies."

Dr. Zev Wainberg and Dr. Siddhartha Mukherjee, clinician and researcher at Columbia University and Pulitzer Prize-winning author of The Emperor of All Maladies and The Gene, will discuss their perspectives on the field of immuno-oncology during today’s virtual R&D Day, which will be available on the Investors section of the corporate website under Events & Presentations. To register, please sign up here.

About LYT-200

LYT-200 is a monoclonal antibody targeting a foundational immunosuppressive protein, galectin-9, for the potential treatment of solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer and cholangiocarcinoma, that are difficult to treat and have poor survival rates. PureTech has presented preclinical data demonstrating high expression of galectin-9 across breast cancer, pancreatic and cholangiocarcinoma samples and found that the highest levels of galectin-9 correlated with shorter time to disease relapse and poor survival. These data suggest that galectin-9 could be significant both as a therapeutic target for a range of cancers and as a cancer biomarker. Preclinical animal and patient-derived organoid tumor models also showed the potential efficacy of LYT-200 and the importance of galectin-9 as a target. LYT-200 is currently being evaluated in a Phase 1/2 adaptive design trial, and results from the Phase 1 portion are expected in the fourth quarter of 2021.

About PureTech’s Virtual R&D Day

The virtual R&D Day will showcase PureTech’s scientific leadership in lymphatics and related immune pathways and detail PureTech’s Wholly Owned Pipeline. Product candidates within this pipeline include LYT-100, a clinical-stage, anti-fibrotic and anti-inflammatory small molecule being advanced for the potential treatment of interstitial lung diseases and lymphedema, LYT-200, a clinical-stage monoclonal antibody targeting foundational immunosuppressive mechanisms for the potential treatment of solid tumors, and LYT-300, an oral form of allopregnanolone that is being advanced into IND-enabling studies for a range of neurological conditions. Additionally, the R&D Day will detail PureTech’s discovery platforms, including the Glyph technology platform, which is designed to target therapeutics to the lymphatic system and potentially enabling oral administration of natural bioactive molecules such as neurosteroids and cannabinoids, and the Orasome technology platform, which is designed to enable the oral administration of biotherapeutics, such as antisense oligonucleotides, short interfering RNA, mRNA, modular expression systems for therapeutic proteins, peptides and nanoparticles.

On December 11, 2020 Nextera reported that the Norwegian Research Council (NRC) has awarded a prestigious 15.7 MNOK grant funding to expand our NextCore platform with a novel T cell receptor (TCR) discovery pipeline (Press release, Nextera, DEC 11, 2020, View Source [SID1234575788]).

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The latest generation immuno-oncology (IO) therapies have shown a remarkable ability to treat and eventually cure cancer by evoking or grafting an anti-cancer immune response into patients. T cells are at the core of this immune response and they acquire this ability through their TCRs. Therefore, further improvements in harnessing IO therapy will critically depend upon the availability of clinically safe and potent TCRs.

"The NextCore phage display platform is uniquely equipped to address the unmet need in therapeutic TCR supply and development. This project is a natural expansion of our already strong T cell immunology focus in drug discovery, and gives Nextera a solid footprint in current and next generation cancer immunotherapies. The grant is instrumental for the initiation of this project, and represents a validation of Nextera’s commercial pathway." Geir Åge Løset, PhD, co-founder and Chief Executive Officer, Nextera AS, commented.