On August 3, 2016 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that it has successfully completed the safety run-in phase of its clinical phase 2 study of MOR208 in combination with lenalidomide in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), the most common form of non-Hodgkin’s lymphoma (NHL). Six patients have been administered MOR208 at the recommended dose (12mg/kg) in combination with lenalidomide during the safety run-in part of the L-MIND study. No unexpected safety signals were detected, and the study will continue as planned.

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"We continue to investigate MOR208 in combination with lenalidomide as a potential treatment for patients with DLBCL. This is part of our broader initiative to develop MOR208 as an antibody backbone for a variety of combination partners. We are pleased with the initial safety run-in results from the L-MIND trial, which showed no unexpected safety signals," commented Dr. Arndt Schottelius, Chief Development Officer of MorphoSys AG. "The clinical trial is progressing as planned, and we expect to present first efficacy data in 2017."

L-MIND is a single-arm, open-label, multicenter study of the anti-CD19 antibody MOR208 in combination with lenalidomide enrolling approximately 80 patients with relapsed or refractory DLBCL after up to two prior lines of therapy, including an anti-CD20 targeting therapy (e.g. rituximab). Patients must not be candidates for high-dose chemotherapy and autologous stem cell transplantation. The study’s primary endpoint is overall response rate (ORR). Secondary outcome measures include duration of response (DoR), progression-free survival (PFS) and overall survival (OS), as well as an evaluation of the drug combination’s safety and pharmacokinetic parameters of MOR208.

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 enhances B cell receptor (BCR) signaling which is important for B cell survival – making CD19 a potential target in B cell malignancies.
MOR208 (previously Xmab5574) is an Fc-enhanced antibody targeting CD19. Fc-enhancement of MOR208 leads to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Furthermore, MOR208 induces direct apoptosis by binding to CD19.
MorphoSys AG is investigating the targeting of BCR-associated CD19 with the Fc-enhanced antibody MOR208 as an immunotherapeutic option in B cell malignancies.
Updated data, presented at the 2016 annual meetings of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and European Hematology Association (EHA) (Free EHA Whitepaper) (ASCO, EHA (Free EHA Whitepaper) 2016), presented the results of efficacy and safety studies of MOR208 as monotherapy in 92 heavily pre-treated NHL patients (non-Hodgkin’s lymphoma). The overall response rate (ORR) in evaluable patients was 36% in the diffuse large B cell lymphoma (DLBCL) and 33% in indolent NHL (iNHL) patients. At the time of the analysis, the median duration of response (DoR) (Kaplan-Meier estimates) in DLBCL was 20 months with 3 ongoing responses. Median DoR was not reached in iNHL patients with 72% of responders without disease progression at 16 months. The 12-months PFS rate in DLBCL was 40% with similar PFS in both rituximab-sensitive and -refractory patients. The incidence of MOR208 treatment-related serious adverse events was 6% in DLBCL and 4% in iNHL patients. No treatment-related deaths were reported.

On August 2, 2016 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Adicet Bio, Inc. reported a collaboration and licensing agreement to develop next-generation engineered immune cell therapeutics (Press release, Regeneron, AUG 2, 2016, View Source [SID:1234514181]). The companies plan to engineer immune cells with fully human chimeric antigen receptors (CARs) and T-cell receptors (TCRs) directed to disease-specific cell surface antigens in order to enable the precise engagement and killing of tumor cells. The collaboration is intended to generate multiple clinical product candidates for various hematological and solid tumor cancers.

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Under the terms of the agreement, Regeneron and Adicet will collaborate to identify and validate appropriate targets and work together to develop a pipeline of engineered immune cell therapeutics for the selected targets. Adicet will receive a $25 million upfront payment, as well as research funding over the course of a five-year research term. Regeneron has the option to obtain development and commercial rights for a certain number of the product candidates, and Adicet has an option to participate in the development and commercialization on these potential products or is entitled to royalty payments by Regeneron. Immune cell therapy product candidates developed and commercialized by Adicet under the agreement will be subject to payment of royalties to Regeneron. Regeneron will have the right to leverage targeting molecules it developed under the collaboration in its other monoclonal and bispecific antibody programs, including those that are part of the Sanofi immuno-oncology collaboration.

"Adicet’s immune cell technology, developed under the leadership of pioneering biotech executive Aya Jakobovits, complements our growing suite of immuno-oncology approaches and therapeutics," said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. "Our proprietary technology platforms give us the ability to develop optimized monoclonal and bispecific antibodies, antibody-drug conjugates and now CARs and TCRs for engineered immune cell therapeutics, opening the door to many different combination approaches to treat cancer patients."

T-cells engineered with tumor targeting molecules, such as CARs and TCRs, are emerging as a potential approach to restore the immune system’s ability to recognize and eradicate tumors. However, there are several limitations to the current approaches for developing engineered T-cell therapeutics. Most approaches rely on ex vivo (outside of the body) editing of the patient’s own immune cells, which creates process variability and logistical challenges. Regeneron and Adicet plan to pursue off-the-shelf cellular therapies. Additionally, while the current engineered product candidates have shown promise in certain blood cancers, such as leukemia and lymphoma, such efficacy in solid tumors is yet to be proven. The cell platform being developed by Adicet and novel targeting approaches to be pursued by the collaborators are aimed at improving access to and killing of solid tumor cells.

"We are excited to join forces with Regeneron, an industry leader in the development of cutting-edge platform technologies and immune-based products," said Aya Jakobovits, Ph.D., President and Chief Executive Officer of Adicet. "The collaboration leverages complementary strengths and technologies of the two companies and expands Adicet’s ability to grow a broad pipeline of novel immune cell products to fight different cancer indications."

On August 2, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the European Commission (EC) has approved KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, at a dose of 2 mg/kg every three weeks, for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen (Press release, Merck & Co, AUG 2, 2016, View Source [SID:1234514180]). Patients with EGFR or ALK positive tumor mutations should also have received approved therapy for these mutations prior to receiving KEYTRUDA. The EC approval allows marketing of KEYTRUDA in all 28 EU member states.

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The approval is based on findings from KEYNOTE-010, a pivotal study which showed KEYTRUDA significantly improved overall survival (OS) compared to standard of care chemotherapy.

"This approval provides an important new treatment regimen for patients in Europe with advanced lung cancer, one of the most common and challenging cancers," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. "In the KEYNOTE-010 trial, patients with advanced lung cancer who had failed prior regimens experienced improved overall survival when treated with KEYTRUDA as compared with those treated with traditional chemotherapy."

"The survival benefit for KEYTRUDA observed in previously-treated patients who express PD-L1 is promising," said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario, Madrid, Spain. "There is a significant unmet need for lung cancer patients, and with this approval, we now have a new personalized treatment option which uses biomarker testing to predict which patients are most likely to benefit from treatment."

About KEYNOTE-010

KEYNOTE-010 is a global, open-label, randomized, pivotal phase 2/3 study evaluating KEYTRUDA (pembrolizumab) (2 mg/kg or 10 mg/kg every three weeks) compared to standard of care chemotherapy (docetaxel, 75 mg/m2 every three weeks) in 1,033 patients with squamous and non-squamous NSCLC who experienced disease progression after platinum-containing systemic therapy and whose tumors expressed PD-L1. The primary endpoints were OS and progression-free survival (PFS) and were assessed based on patients with any level of PD-L1 expression (greater than or equal to one percent) and in patients whose tumors express higher levels of PD-L1 (greater than or equal to 50 percent) – as reflected by tumor proportion score (TPS).

In the total study population (all levels of PD-L1 expression), both doses of KEYTRUDA studied significantly improved OS compared with docetaxel. Specifically, KEYTRUDA resulted in a 29 percent improvement in OS for the 2 mg/kg dose (HR 0.71 [95% CI, 0.58-0.88; P=0.001]) and a 39 percent improvement in OS for the 10 mg/kg dose (HR 0.61 [95% CI, 0.49-0.75; P<0.001]), compared to docetaxel. Median OS for KEYTRUDA was 10.4 months (95% CI, 9.4-11.9) and 12.7 months (95% CI, 10.0-17.3), respectively, compared to 8.5 months for docetaxel (95% CI, 7.5-9.8).

Among patients with higher levels of PD-L1 expression (a TPS score of 50 percent or greater), OS was superior for both KEYTRUDA doses compared with docetaxel. Specifically, KEYTRUDA improved OS by 46 percent for the 2 mg/kg dose (HR 0.54 [95% CI, 0.38-0.77; P=0.001]) and by 50 percent for the 10 mg/kg dose (HR 0.50 [95% CI, 0.36-0.70; P<0.001]), compared to docetaxel. Median OS for KEYTRUDA (2 mg/kg and 10 mg/kg, respectively) was 14.9 months (95% CI, 10.4 to not reached) and 17.3 months (95% CI, 11.8 to not reached), compared to 8.2 months for docetaxel (95% CI, 6.4-10.7).

Among patients in the total study population treated with KEYTRUDA (2 mg/kg and 10 mg/kg, respectively), median PFS was 3.9 months (95% CI, 3.1-4.1) and 4.0 months (95% CI, 2.6-4.3), compared to 4.0 months for docetaxel (95% CI, 3.1-4.2). KEYTRUDA numerically reduced the risk of progression or death (PFS) at both doses (HR 0.88 [95% CI, 0.73-1.04] for 2 mg/kg; HR 0.79 [95% CI, 0.66-0.94] for 10 mg/kg). PFS results in the overall population were not statistically significant for either dose based on protocol-specified statistical testing requirements.

Patients with higher levels of PD-L1 expression who were treated with KEYTRUDA had significantly prolonged PFS compared to docetaxel (HR 0.58 [95% CI, 0.43-0.77; P=0.001] for 2 mg/kg; HR 0.59 [95% CI, 0.45-0.78; P<0.001] for 10 mg/kg). Among patients treated with KEYTRUDA (pembrolizumab) (2 mg/kg and 10 mg/kg, respectively), median PFS was 5.2 months (95% CI, 4.0-6.5) and 5.2 months (95% CI, 4.1-8.1), compared to 4.1 months for docetaxel (95% CI, 3.6-4.3).

The safety analysis supporting the European approval of KEYTRUDA was based on 2,799 patients with advanced melanoma or NSCLC across three doses (2 mg/kg every three weeks or 10 mg/kg every two or three weeks) in studies KEYNOTE-001, KEYNOTE-002 and KEYNOTE-010 combined. The most common adverse reactions (>10%) with KEYTRUDA were fatigue (24%), rash (19%), pruritus (18%), diarrhea (12%), nausea (11%) and arthralgia (10%). The majority of adverse reactions reported were of Grade 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions.

"We are thrilled that the European Union will now have a new treatment option for certain patients with advanced non-small cell lung cancer who have not responded to chemotherapy," said Stefania Vallone, president, Lung Cancer Europe. "Lung cancer represents the leading cause of cancer death worldwide, and this milestone underscores the importance of innovation and commitment to developing new treatments that can have a positive impact for patients living with this disease."

About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon, breast, and prostate cancers combined. The two main types of lung cancer are non-small cell and small cell. NSCLC is the most common type of lung cancer, accounting for about 85 percent of all cases. The five-year relative survival rate for patients suffering from highly advanced, metastatic (Stage IV) lung cancers is estimated to be two percent.

About KEYTRUDA (pembrolizumab) Injection 100 mg in the U.S.

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA (pembrolizumab) is also indicated for the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

KEYTRUDA is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every three weeks for the approved indications.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Immune-mediated pneumonitis occurred in 19 (3.5%) of 550 patients, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis and occurred more frequently in patients with a history of asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic radiation (6.0%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-mediated colitis occurred in 4 (0.7%) of 550 patients, including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 1 (0.2%) of 550 patients, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

Hyperthyroidism occurred in 10 (1.8%) of 550 patients, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3 (0.1%) of 2117 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA (pembrolizumab) and administer anti-hyperglycemics in patients with severe hyperglycemia.

Immune-mediated nephritis occurred in patients receiving KEYTRUDA. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.

Severe and life-threatening infusion-related reactions have been reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).

No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA (pembrolizumab).

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 300 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On August 2, 2016 Foundation Medicine, Inc. (NASDAQ: FMI) reported that the U.S. Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS) have accepted FoundationOne for Parallel Review as an innovative technology most likely to benefit from the efficiencies of this program (Press release, Foundation Medicine, AUG 2, 2016, View Source [SID:1234514179]). The FDA also accepted Foundation Medicine’s request for review as part of its Expedited Access Pathway (EAP) for breakthrough devices.

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If approved, FoundationOne could be the first FDA-approved comprehensive genomic profiling (CGP) assay to incorporate multiple companion diagnostics (CDx) to support precision medicine in oncology, including an indication for use as a companion diagnostic across a diverse range of solid tumors. Importantly, obtaining a Medicare National Coverage Determination (NCD) from CMS concurrently with FDA approval will allow FoundationOne to be offered as a covered benefit under Medicare and avoid the significant time interval and uncertainty that often occurs between FDA approval and an NCD. Based on discussions with FDA and CMS, Foundation Medicine believes the Parallel Review will conclude in the second half of 2017.

"The acceptance of FoundationOne for EAP and Parallel Review is a significant advancement towards the achievement of precision medicine, enhancing patient access to targeted therapies and clinical trials," said Michael Pellini, M.D., chief executive officer of Foundation Medicine. "While we proceed with FDA and CMS, we will continue our work with Palmetto GBA, our Medicare Administrative Contractor (MAC) in North Carolina and a recognized thought leader in molecular diagnostics. We will also continue our work with the MAC in Massachusetts, National Government Services (NGS). Specifically, we will work with Palmetto through its MolDx Program to expand coverage of well-validated CGP assays, such as FoundationOne, to include additional cancer indications beyond the existing local coverage determination (LCD), which currently covers a subset of patients with non-small cell lung cancer (NSCLC). Pursuing avenues at both the local and national levels maximizes the opportunity for Medicare beneficiaries with cancer to have access to FoundationOne."

FoundationOne is a CGP assay for cancer that uniquely detects genomic alterations, including substitutions, insertions and deletions, copy number alterations and select gene rearrangements in 324 genes using DNA isolated from formalin-fixed paraffin-embedded tumor tissue specimens using next-generation sequencing and computational analysis. It is intended that FoundationOne, if approved, will be used to identify patients who may benefit from treatment for solid tumor malignancies in accordance with FDA approval. FoundationOne will also be intended to provide treating physicians with important information, including cancer related variants and molecular signatures to inform molecular eligibility for clinical trials or treatment management according to clinical care guidelines.

Dr. Pellini continued, "Beyond its application in cancer care, an FDA-approved FoundationOne incorporating multiple companion diagnostics would provide a significant and highly differentiated offering for our biopharma partners. We believe this approach, which is designed to expedite approval of additional biomarkers on FoundationOne, both accelerates and de-risks companion diagnostic approval for our biopharma partners seeking a coordinated regulatory strategy for therapeutic drug approval."

Parallel Review provides for concurrent review of medical devices for FDA approval and a national coverage determination by CMS to facilitate patient access to innovative medical devices. The FDA granted Foundation Medicine’s request for EAP because it met the three criteria necessary for inclusion in the program, one of which is the large unmet need for comprehensive genomic profiling of tumors. Under the EAP, the FDA works with device sponsors to try to reduce the time and cost from development to an approval decision.

On August 2, 2016 Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), a biopharmaceutical company developing oral therapies that target various phases of cell cycle control for the treatment of cancer and other serious disorders reported the publication of a paper by researchers at Yale University with promising preclinical data related to CYC065, Cyclacel’s second generation cyclin-dependent kinase CDK2/9 inhibitor (Press release, Cyclacel, AUG 2, 2016, View Source [SID:1234514176]). The paper, titled "Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo" is published in the July 2016 issue of the British Journal of Cancer (www.nature.com/bjc/journal/v115/n3/abs/bjc2016198a.html).

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In this investigator-sponsored preclinical study, the authors investigated the potential of cyclin E1 (CCNE1) amplification and PIK3CA driver mutations, both common in uterine serous carcinoma (USC), as therapeutic targets. The paper demonstrated that CYC065, alone and in combination with the investigational PIK3CA inhibitor taselisib, may have potential as a treatment option in USC.

The authors found that 89.5% of USC tumor samples overexpressed the cyclin E1 (CCNE1) gene, which transcribes the cyclin E partner of CDK2, and is responsible for cellular proliferation. As a potent and selective CDK2/9 inhibitor, CYC065 was investigated as a new treatment option for this aggressive type of endometrial cancer. The researchers reported that CYC065 not only inhibited cellular proliferation of CCNE1-amplified USC models in vitro but also reduced tumor growth in murine xenograft models. Importantly, the researchers found CCNE1 expression to significantly correlate with sensitivity to CYC065 in vitro and the cellular mechanism of action, namely accumulation of cells in G1 phase, was consistent with inhibition of the CDK2-cyclin E complex in CCNE1 amplified USC cell lines.

Furthermore, mutations to the Her2/PI3K/AKT/mTOR signaling pathway frequently coincide with CCNE1-amplifications in USC. To address this form of USC, the researchers reported, that combination treatment using CYC065 and the investigational PI3KCA inhibitor, taselisib, was synergistic, resulting in a significant reduction in tumor growth in murine xenograft models of CCNE1-amplified/PIK3CA-mutated USC.

"Treatment options for patients with these aggressive endometrial cancers are limited," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel, "we are encouraged by these preclinical data showing that CYC065 alone or in combination inhibits USC tumor growth. Upregulation of CCNE1 has been reported for many human cancers, including breast, colon, gastric, lung and high-grade ovarian, and has been correlated with poor prognosis and drug resistance. These findings provide strong rationale for the use of CYC065 to target the CDK2-cyclin E complex in such cancers and warrants further investigation in tumors with amplified/overexpressed CCNE1. The findings are consistent with previously reported preclinical data that CYC065 reverses cyclin E-mediated resistance to trastuzumab in breast cancer. We look forward to reporting data from the ongoing first-in-human, Phase 1 study of CYC065 in solid tumors and lymphomas."

About CYC065

CYC065 is a highly-selective, orally- and intravenously-available, second generation inhibitor of CDK2 and CDK9 and causes apoptotic death of cancer cells at sub-micromolar concentrations. Antitumor efficacy has been achieved in vivo with once a day oral dosing at well tolerated doses. Evidence from published nonclinical studies show that CYC065 may benefit patients with adult and pediatric hematological malignancies, including certain Acute Myeloid Leukemias (AML), Acute Lymphocytic Leukemias (ALL), Chronic Lymphocytic Leukemias (CLL), B-cell lymphomas, multiple myelomas, and certain solid tumors, including breast and uterine cancers. Independent investigators published nonclinical evidence that CYC065 induced regression or tumor growth inhibition in a model of HER2-positive breast cancer addicted to cyclin E that is resistant to trastuzumab (Herceptin), and that CYC065 reduced tumor growth in models of CCNE1-amplified uterine serous carcinoma.

CYC065 is mechanistically similar but has much higher dose potency, in vitro and in vivo, improved metabolic stability and longer patent protection than seliciclib, Cyclacel’s first generation CDK inhibitor. Translational biology data support development of CYC065 as a stratified medicine for solid and liquid cancers. CYC065 has been shown to reverse drug resistance associated with the addiction of cancer cells to cyclin E and may inhibit CDK9-dependent oncogenic and leukemogenic pathways, including malignancies driven by certain oncogenes and mixed lineage leukemia rearrangements (MLL-r). CYC065 causes prolonged down regulation of the Mcl-1-mediated pro-survival pathway in cancer cells.