On March 27, 2019 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company") a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported its financial results and business highlights for the fourth quarter and full year ended December 31, 2018 (Press release, Cyclacel, MAR 27, 2019, View Source [SID1234534660]). The Company’s net loss applicable to common shareholders for the three months and year ended December 31, 2018 was $2.1 million and $7.5 million, respectively. As of December 31, 2018, cash and cash equivalents totaled $17.5 million, not including net proceeds of approximately $4.1 million from a Common Stock Sales Agreement.

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"We are executing on our targeted oncology strategy with the objective of delivering data readouts from multiple clinical programs," said Spiro Rombotis, President and Chief Executive Officer. "At the heart of our business strategy is targeting patients with overexpression of cancer resistance proteins, including Mcl-1, MYC, cyclin E, and inherited mutations in DNA damage pathways, such as BRCA. We believe CYC065 is the first investigational drug to have consistently demonstrated durable suppression of Mcl-1 at tolerable dosing in patients. We have treated patients in two out of four studies under our MD Anderson collaboration, the Phase 1 study of a combination of CYC065 and venetoclax in relapsed/refractory CLL and the first-in-human, Phase 1 study of CYC140 in advanced leukemias. Protocols for the other two studies have been finalized and will be submitted to institutional review boards. The first two patients with BRCA mutant breast cancer were treated in the sapacitabine and olaparib IST. With estimated capital on hand until the end of 2020 we look forward to reporting data from our ongoing clinical studies and realizing shareholder value from our targeted drug pipeline."

Fourth Quarter and Full-Year Highlights

Drug Development

CYC065 CDK Inhibitor

Initiated a Phase 1 clinical trial evaluating CYC065, a CDK2/9 inhibitor, in combination with venetoclax in patients with relapsed/refractory CLL. The first patient has been treated with this dose regimen without dose-limiting toxicity. The strong biological rationale of dual Mcl-1 and Bcl-2 suppression was presented at the 2018 AACR (Free AACR Whitepaper) in a poster titled "Strategic combination of the cyclin-dependent kinase inhibitor CYC065 with venetoclax to target anti-apoptotic proteins in chronic lymphocytic leukemia." The data showed an enhanced effect of the combination of CYC065 and venetoclax in CLL tumor samples, including demonstrating activity in 17p deleted samples which were resistant to either agent alone.

Data from the Phase 1 part 1 clinical study of CYC065 monotherapy administered intravenously over 4 hours every 3 weeks in patients with advanced solid tumors were reported at an oral presentation at the 2018 AACR (Free AACR Whitepaper). Prolonged reduction of Mcl-1 expression was observed in 11 out of 13 patients treated at the recommended Phase 2 dose (RP2D) following a single dose of CYC065. Cyclacel continues to enroll patients in part 2 of the study evaluating CYC065 in a more intensive schedule for 2 days per week over 2 weeks of a three-week cycle. Part 3 of the study is planned to evaluate an oral CYC065 formulation.

Discussions with principal investigators and/or cooperative groups progressed with the objective of evaluating CYC065 in patients with certain hematological malignancies and solid tumors.

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DNA Damage Response (DDR) Program

The first two patients have been dosed in the Phase 1b/2 investigator-sponsored study of sapacitabine in combination with olaparib, an approved PARP inhibitor, in patients with BRCA mutant breast cancer. According to the investigators both patients achieved tumor shrinkage. Dual targeting of the DNA damage response pathway with the addition of sapacitabine to olaparib may enhance the efficacy of the current standard of care for such patients.

Patient enrolment has continued in part 3 of a Phase 1 study evaluating a revised dosing schedule of sequential sapacitabine and seliciclib, Cyclacel’s first-generation CDK inhibitor, in BRCA mutation positive patients with advanced breast, ovarian and pancreatic cancer. New data on an expanded cohort from part 1 of this study will be the subject of a poster titled "Expansion cohort of Phase I study of oral sapacitabine and oral seliciclib in patients with metastatic breast cancer and BRCA1/2 mutations" at the 2019 AACR (Free AACR Whitepaper).

CYC140 PLK1 Inhibitor

The first patient has been dosed in a Phase 1 first-in-human study evaluating CYC140 in patients with advanced leukemias. CYC140 is a small molecule, selective polo-like-kinase 1 (PLK1) inhibitor that has demonstrated potent and selective target inhibition and high activity in xenograft models of human cancers.

SEAMLESS Phase 3 Study

Stratified and exploratory subgroup analyses have defined a subgroup of patients for whom the sapacitabine regimen may represent an improvement over low intensity treatment by decitabine alone. Following consultation with three European regulatory authorities regarding a potential approval pathway for sapacitabine the Company intends to submit a request for scientific advice to the Scientific Advice Working Party (SAWP) of the European Medicines Agency.

Corporate Developments

Entered into a collaboration with The University of Texas MD Anderson Cancer Center to evaluate three Cyclacel medicines in patients with hematological malignancies. MD Anderson will evaluate CYC065, CYC140 and sapacitabine either as single agents or in combination with approved drugs, in up to 170 enrolled patients across four clinical trials.

Added Robert J. Spiegel, M.D. to the Company’s Board of Directors. Dr. Spiegel brings over 30 years of R&D and operational experience in the biopharmaceutical industry as well as advisory experience to venture capital and private equity funds.

Entered into a Common Stock Sales Agreement with H.C. Wainwright & Co., LLC as sales agent, pursuant to which the agent may sell shares of common stock having an aggregate offering price of up to $5.0 million by any method that is deemed to be an "at the market offering" as defined in Rule 415 under the Securities Act of 1933 as amended.

2019 Key Upcoming Business Objectives

·Report expansion cohort, Phase 1 clinical data with an oral sequential regimen of sapacitabine and seliciclib in patients with BRCA mutant metastatic breast cancer at the 2019 AACR (Free AACR Whitepaper)
·Initiate CYC065-venetoclax Phase 1 study in patients with relapsed or refractory AML or MDS
·Initiate sapacitabine-venetoclax Phase 1 study in patients with relapsed or refractory AML or MDS
·Report initial data from the CYC065-venetoclax Phase 1 studies in leukemias

·Report initial data from the CYC140 Phase 1 First-in-Human study
·Report initial data and bioavailability from the Phase 1 study of an oral formulation of CYC065
·Report updated CYC065 Phase 1 data in patients with advanced solid cancers
·Report data from the IST Phase 1b/2 trial of sapacitabine-olaparib combination in patients with BRCA mutant metastatic breast cancer when reported by the investigators
·Determine regulatory pathway and submissibility of sapacitabine in elderly AML

Financial Highlights

As of December 31, 2018, cash and cash equivalents totaled $17.5 million, compared to $23.9 million as of December 31, 2017. The decrease of $6.4 million was primarily due to net cash used in operating activities of $6.7 million, net cash used in investing activities of $0.1 million, offset by $0.4 million of net cash provided by financing activities.

Revenues for the three months and year ended December 31, 2018 amounted to $0.2 million compared to nil revenue for the same periods in 2017. The revenue is related to a June 2015 collaboration, licensing and supply agreement with ManRos Therapeutics SA.

Research and development expenses were $1.1 million and $4.3 million for the three months and year ended December 31, 2018 as compared to $0.7 million and $4.2 million for the same periods in 2017. Research and development expenses relating to transcriptional regulation increased by $1.5 million from $1.1 million for the year ended December 31, 2017 to $2.5 million for the year ended December 31, 2018, as the clinical evaluation of CYC065 progresses. Research and development expenses relating to sapacitabine decreased by $1.7 million from $2.5 million for the year ended December 31, 2017 to $0.8 million for the year ended December 31, 2018, primarily as a result of a reduction in expenditures associated with the SEAMLESS Phase 3 trial and related costs.

General and administrative expenses for the three months and year ended December 31, 2018 were $1.5 million and $5.3 million, respectively compared to $1.5 million and $5.3 million for the same period of the previous year.

Total other income, net for the three months and year ended December 31, 2018 were $0.1 million and $0.9 million, compared to $0.1 million and $1.0 million for the same period of the previous year. The decrease of $0.1 million for the year ended December 31, 2018 is primarily related to a reduction in income received under an Asset Purchase Agreement with ThermoFisher Scientific Company and offset by a $0.2 million increase in interest income.

United Kingdom research & development tax credits were $0.4 million and $1.3 million for the three months and year ended December 31, 2018 as compared to $0.2 million and $1.0 million for the same periods in 2017.

Net loss for the three months and year ended December 31, 2018 were $2.0 million and $7.3 million compared to $1.9 million and $7.5 million for the same periods in 2017.

The Company raised net proceeds of approximately $4.7 million, of which $4.1 million was received in 2019, from its Common Stock Sales Agreement with H.C. Wainwright. This agreement is now complete. Together with cash resources of $17.5 million as of December 31, 2018 the Company estimates cash resources will fund currently planned programs through the end of 2020.

Conference call information:

US/Canada call: (877) 493-9121 / international call: (973) 582-2750

US/Canada archive: (800) 585-8367 / international archive: (404) 537-3406

Code for live and archived conference call is 9719419.

For the live and archived webcast, please visit the Corporate Presentations page on the Cyclacel website at www.cyclacel.com. The webcast will be archived for 90 days and the audio replay for 7 days

On March 27, 2019 Eureka Therapeutics, Inc., a clinical stage biotechnology company developing novel T-cell therapies that harness the evolutionary power of the immune system, reported the publication of a proof-of-concept study in Science Translational Medicine entitled "GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR-T cells (Press release, Eureka Therapeutics, MAR 27, 2019, View Source [SID1234534677])." The study was led by researchers from Eureka, Memorial Sloan Kettering Cancer Center (MSK) and Juno Therapeutics (Juno).

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Antibody-based therapies, including bi-specific antibodies and chimeric antigen receptor (CAR) T-cell therapies targeting B cell maturation antigen (BCMA) for multiple myeloma, have shown promising clinical results, but relapses associated with low-to-negative expression of BCMA have been reported, necessitating additional targets for multiple myeloma.

The orphan G protein-coupled receptor GPRC5D has been previously identified in bone marrow cells in patients with multiple myeloma. However, the protein expression profile of GPRC5D remained elusive. Through immunohistochemical analyses, the study demonstrated that GPRC5D is expressed on malignant bone marrow plasma cells, while normal tissue expression is limited to the hair follicle, an immune-privileged site.

In 83 evaluated primary myeloma marrow samples, 65% of samples have GPRC5D expression above a 50% antigen expression cutoff on CD138+ cells. More importantly, GPRC5D expression on CD138 multiple myeloma cells was independent of BCMA expression, suggesting GPRC5D as an ideal clinical target.

In collaboration with MSK, Eureka developed antibodies targeting GPRC5D using Eureka’s proprietary E-ALPHA discovery platform. These antibodies, together with antibodies targeting BCMA and another undisclosed multiple myeloma target, were licensed by Eureka and MSK to Juno (now Celgene) in 2016 for use in CARs.

In a head-to-head comparison with BCMA-targeted CARs with an identical backbone, GPRC5-targeted CAR-T cells demonstrated efficient antigen-specific cytotoxicity in vitro, as well as comparable effect in inducing tumor regression and extending survival at different dose levels in vivo. The study further showed that tumor escape can be rescued by GPRC5D-targeted CAR T-cells in a model of BCMA-antigen loss mediated relapse.

"The study confirms GPRC5D as a viable target in multiple myeloma," said Eric Smith, M.D., Ph.D., a medical oncologist and the Director of Clinical Translation within the Cellular Therapeutics Center at MSK. "We look forward to moving this study into the clinic, including in relapsed patients after BCMA-targeted therapy."

"Targeting GPRC5D has the potential to improve the durability of response from current bi-specific and T-cell therapies that target only BCMA," said Dr. Cheng Liu, President and Chief Executive Officer at Eureka Therapeutics. "This study reflects our commitment to increasing the long-term clinical benefit for patients with multiple myeloma and other cancers, and we look forward to leveraging our E-ALPHA and ARTEMIS platforms to develop transformational new T-cell therapies that are potentially safer and more effective."

On March 27, 2019 Elicio reported that it launched with $30 million in funding and an immunotherapy strategy aimed at getting cancer vaccines into the lymph nodes, a location that orchestrates immune responses but has been hard to target directly (Press release, Elicio Therapeutics, MAR 27, 2019, View Source [SID1234534871]).

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Elicio Therapeutics (Cambridge, Mass.) has exclusively licensed the Amphiphile platform from Darrell Irvine at the Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology. Irvine’s group figured out in 2014 how to ferry cancer vaccines into lymph nodes by tethering the vaccines to albumin to "hitchhike" on the carrier’s normal transportation route (see "Hitchhiker’s Guide to the Lymph Node").

Irvine’s group noticed that albumin effectively carried dyes and other compounds into the lymph nodes. In preclinical studies, the team showed that by conjugating vaccines to an albumin-binding lipid tail, tumor-targeting antigens and adjuvants elicited strong immune responses and slowed or reduced tumor growth in mice.

Elicio’s lead candidates from the Amphiphile platform will target pancreatic, colorectal and head and neck cancers. CEO Robert Connelly told BioCentury that Elicio is developing cancer vaccines with a range of different types of shared antigens, including viral antigens.

Connelly said the antigens Elicio is using "have only been delivered systemically, not directly to the lymph nodes," which results in weak immune responses and occasional systemic toxicity. "This is why cancer vaccines have been disappointing to date," he added.

Elicio plans to begin a Phase I/II trial in early 2020 of VED-002, a vaccine targeting KRAS mutations, to treat pancreatic cancer. Its second candidate, VED-001, is a vaccine targeting HPV E6 and E7 transforming proteins. It is set to enter the clinic in 2020 as a single agent and in combination with a checkpoint inhibitor for HPV-positive head and neck cancers.

Connelly declined to disclose the company’s investors.

Connelly was previously a venture partner at Flagship Pioneering and has served as CEO of multiple companies, including pulmonary disease company Pulmatrix Inc. (NASDAQ:PULM) from 2007 to 2012 and metabolic dysregulation company Axcella Health Inc. (Cambridge, Mass.) from 2013 to 2018.
Irvine is a professor of materials science and engineering and of biological engineering at MIT.

Targets: E6 transforming protein (Human papillomavirus-16) – HpV16gp1; E7 transforming protein (Human papillomavirus-16) – HpV16gp2; KRAS – K-Ras

On March 27, 2019 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on using the body’s immune system to fight cancer, reported that it will participate in a panel presentation discussing the latest science in immunotherapy at a two day symposium titled, "Frontiers in Cancer Immunotherapy," hosted by the New York Academy of Sciences on May 14–15, 2019 (Press release, Anixa Biosciences, MAR 27, 2019, View Source [SID1234534661]).

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The panel presentation, "Will CAR-T cell Therapies, Bispecific Antibodies or TILs be more Beneficial for Solid Tumors?" will focus on a discussion about immunotherapy’s potential for addressing solid tumors. Additional panel participants include Renier Brentjens, MD, PhD, Memorial Sloan Kettering Cancer Center, and Maria Fardis, PhD, MBA, Iovance Biotherapeutics. Other speakers at the conference include James Allison, PhD, MD Anderson Cancer Center, Philip Greenburg, MD, Fred Hutchison Cancer Center and Lisa Butterfield, PhD, The Parker Institute for Cancer Immunotherapy.

Dr. Sara Donnelly, Program Manager at the Academy and conference organizer said, "Immuno-oncology promises a revolution in the way we treat cancer. This two-day symposium will convene leading experts in cancer immunotherapy to discuss cutting-edge findings in the broad area of combination therapies, including checkpoint inhibitors and cellular therapies." More information about the meeting, other participants, and registration can be found at: View Source

On March 27, 2019 Bio-Thera Solutions, a clinical-stage biopharmaceutical company developing a pipeline of innovative oncology therapies and a pipeline of biosimilars, reported the company will present two posters at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting taking place March 29 – April 3, 2018 in Atlanta, Georgia (Press release, BioThera Solutions, MAR 27, 2019, View Source [SID1234534678]).

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The first poster, entitled "BAT8001, a potent anti-HER2 antibody drug conjugate with a novel uncleavable linker to reduce toxicity for patients with HER2-positive tumor," will highlight Phase I clinical data demonstrating the safety and efficacy of BAT8001 in HER2-positive cancer patients. An abstract of the presentation will be available on AACR (Free AACR Whitepaper) website on the day of the presentation.

Presentation details are as follows:

Session Category: Clinical Trials
Session Title: Phase I Clinical Trials: Part 2
Session Date and Time: Monday, April 1, 2019, 8:00 AM – 12:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 17
Poster Board Number:
Abstract Number:

10
CT053

The second poster, entitled "Development of a potent Trop-2 antibody-drug conjugate, BAT8003, for the treatment of Trop-2 positive gastric tumors," will present preclinical data that highlight advantages of BAT8003 as a potential treatment for gastric cancer patients. The IND for a Phase I clinical trial evaluating the safety and pharmacokinetics of BAT8003 was approved earlier this year by the China NMPA. Dosing of the first patient in this Phase I clinical trial is expected to occur during April 2019. An abstract of the presentation is currently available on AACR (Free AACR Whitepaper) website.

Presentation details are as follows:

Session Category: Experimental and Molecular Therapeutics
Session Title: Targeted Therapies
Session Date and Time: Wednesday Apr 3, 2019 8:00 AM – 12:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 14
Poster Board Number:

9

Abstract Number:

4821

Copies of both posters will be made available on the Company’s website after they are presented.

About BAT8001

BAT8001 is an investigational HER2-ADC being evaluated in multiple tumor types. HER2 is a naturally occurring receptor that is overexpressed in many types of cancer, including breast cancer and gastric cancer. BAT8001 is being developed for use as a single agent and in combination with other agents for the treatment of multiple cancers. BAT8001 is currently being evaluated as a single agent in a Phase III metastatic breast cancer trial and in combination with an anti-PD1 antibody in gastric cancer. Both clinical studies are being run in China.

About BAT8003

BAT8003 is an investigational Trop2-ADC being evaluated in multiple tumor types. Trop-2 is a naturally occurring receptor that is overexpressed in many types of cancer, including triple negative breast cancer and gastric cancer. BAT8003 utilizes Bio-Thera Solutions’ proprietary linker-payload combination, Batansine. The antibody component of BAT8003 is engineered for site-specific conjugation to allow for better control of the ADC DAR, providing a more homogenous product. The linker is non-cleavable ensuring superior delivery of the payload to the cancer cells and improving the safety profile of the ADC. BAT8003 is being developed for use as a single agent and in combination with other agents for the treatment of Trop2 positive cancers. A Phase I clinical trial evaluating the pharmacodynamics and safety of BAT8003 will begin dosing patients during April 2019.