On January 5, 2023 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported a business update reviewing 2022 achievements and outlining the Company’s key business objectives for 2023 (Press release, Cyclacel, JAN 5, 2023, View Source [SID1234625917]).

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"2022 was a year of solid progress for Cyclacel highlighted by the clinical advancement of our two product candidates in Phase 1/2 clinical studies," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "Both fadraciclib, our CDK2/9 inhibitor, and plogosertib (formerly CYC140), our PLK1 inhibitor, have shown differentiated and competitive profiles in their respective classes. We believe that fadra is the only transcriptionally active CDK inhibitor to have shown single agent responses in both liquid and solid tumors with a good tolerability profile. We are seeing preliminary indications of single-agent activity in the ongoing Phase 1/2 trial of plogosertib in advanced solid tumors and lymphoma. We also estimate that our cash runway will fund operations through the end of 2023, providing sufficient funding over this catalyst-rich period."

"We believe that we are very close to identifying the recommended Phase 2 dose (RP2D) in the ongoing Phase 1/2 study of oral fadra for the treatment of advanced solid tumors and lymphoma," said Dr. Mark Kirschbaum M.D., Chief Medical Officer. "Fadra is showing signs of single agent activity in several tumor types including PRs in 2/3 T cell lymphoma patients and stable disease in certain solid tumors. Oral fadra has also maintained an acceptable safety and tolerability profile across multiple dosing cohorts. We expect to enter the Phase 2 segment of the trial in the first half of 2023, after completing the rapid accrual we have seen in Phase 1, and reviewing the safety, pharmacokinetics and correlative study data. To accelerate Phase 2 enrollment, we have expanded the number of clinical trial sites participating in the trial including certain widely recognized U.S. and international cancer centers. We expect to provide a data update at a major medical meeting in the first half of 2023 and initial data from the Phase 2 in the second half of 2023."

"We have also made encouraging progress with our second candidate, plogosertib," continued Dr. Kirschbaum. "The dose escalation stage of our Phase 1/2 study in advanced solid tumors and lymphoma is enrolling well. Based upon the molecule’s differentiated profile and early observation of efficacy with three patients on treatment for at least 3 cycles, we believe plogosertib has the potential to demonstrate single-agent activity across a broad range of cancers. We anticipate reporting preliminary safety and efficacy data from the dose-escalation stage of the ongoing plogosertib Phase 1/2 study within 2023."

2022 Key Achievements

Fadraciclib

Final dose-escalation level 6a to determine RP2D in the oral fadraciclib 065-101 Phase 1/2 study has enrolled 3 out of 6 patients
Broad activity observed in the first 5 dose levels: 2/3 partial responses (PRs) in patients with T-cell lymphoma; 4 patients with cervical, endometrial, hepatocellular and ovarian cancer showed stable disease with target lesion reductions; and a patient with pancreatic cancer achieved stable disease for 5 cycles
Achieved target engagement levels predicted to inhibit CDK2 and CDK9 for approximately 5 to 7 hours per dose on continuous dosing
At the Company’s R&D Day a principal investigator from Seoul National University Hospital showed preclinical data demonstrating sensitivity to fadra in biliary tract and pancreatic cancer cells obtained from patient specimens
A publication from The University of Texas MD Anderson Cancer Center reported preclinical data against chronic lymphocytic leukemia (CLL) cell lines showing that fadraciclib, as a single agent and in combination with the BCL2 antagonist, venetoclax, depletes anti-apoptotic proteins and synergizes with venetoclax
Reported positive preliminary data from the Phase 1/2 clinical trial of oral fadraciclib in patients with solid tumors and lymphoma at the ENA 2022 meeting

Plogosertib (formerly CYC140)

Announced dosing of first patient in Phase 1/2 study of oral plogosertib in patients with advanced solid tumors and lymphomas
No dose limiting toxicities observed to date in the first 3 dose levels
Stable disease at the first dose level in an ongoing patient with metastatic, KRAS G12V mutated, non-small cell lung cancer for 9 cycles and a patient with metastatic ovarian cancer for 5 cycles

Corporate Highlights

On October 31, 2022 the Company held an R&D Day (Webcast replay) at which updated clinical and preclinical data on fadraciclib and plogosertib were presented
Announced the election by the preferred stockholders of Kenneth M. Ferguson, Ph.D. to the Board of Directors

Key Business Objectives for 2023

1H 2023

First patient dosed with oral fadraciclib in Phase 2 proof-of-concept stage of 065-101 study in patients with advanced solid tumors and lymphoma
Report final data from dose escalation stage and RP2D determination from the 065-101 study of oral fadraciclib in patients with advanced solid tumors and lymphoma at a major medical meeting
Report interim Phase 1 data from 140-101 study of oral plogosertib in patients with advanced solid tumors and lymphoma
2H 2023

Report interim data from initial cohorts in Phase 2 proof-of-concept stage of 065-101 study with oral fadraciclib in patients with advanced solid tumors and lymphoma
Report interim data from dose escalation stage of 065-102 study with oral fadraciclib in patients with advanced leukemia
Report final data from dose escalation stage of 140-101 study with oral plogosertib in advanced solid tumors and lymphoma

On January 5, 2023 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immune-oncology technologies addressing hard to treat oncology indications, reported that Jeffrey Eisenberg, Chief Executive Officer of Xenetic Biosciences will present at the Virtual Investor 2023 Companies to Watch Event on Tuesday, January 17, 2023 at 10:00 AM ET (Press release, Xenetic Biosciences, JAN 5, 2023, View Source [SID1234625916]).

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A live video webcast of the presentation will be available on the Events page in the Investors section of the Company’s website (www.XeneticBio.com). A webcast replay will be available two hours following the live presentation and will be accessible for 90 days.

About Xene

On January 5, 2023 Caris Life Sciences (Caris), the leading molecular science and technology company actively developing and delivering innovative solutions to revolutionize healthcare, reported the expansion of Caris Discovery, a proprietary, multi-omics target discovery engine designed to unlock otherwise inaccessible targets in areas of high unmet clinical need, with a goal of delivering transformational patient impact (Press release, Caris Life Sciences, JAN 5, 2023, View Source [SID1234625915]).

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Caris Discovery is a disease-agnostic discovery engine that aims to identify novel drug targets through the combination of its differentiated capabilities and assets, including the interrogation of primary patient tissue, a proprietary aptamer-based proteomic profiling platform, unparalleled in silico analyses, and cutting-edge research experimentation at Caris’ dedicated 59,000 square foot Target Discovery Lab.

"Despite numerous breakthroughs in oncology, many patients with cancer desperately need novel medicines to improve their outcomes and quality of life. Discovering new cancer medicines remains extremely challenging, and one of the biggest stumbling blocks is the scarcity of viable targets," said David Spetzler, M.S., Ph.D., MBA, President and Chief Scientific Officer of Caris Life Sciences. "Building on our strength in molecular profiling, our unparalleled repository of real-world patient samples and our industry-leading clinico-genomic database, we have spent years investing in the formation of Caris Discovery, an unmatched platform to identify and validate differentiated, modality-agnostic targets for for the development of precision medicines and therapies."

Caris’ proprietary ADAPT biotargeting system is able to identify many cancer-specific proteins that would elude classical identification methods, increasing the potential to identify truly novel targets. ADAPT deploys an extensive and unbiased library of aptamers – single-stranded molecules of DNA that can bind to almost any cellular target – to uncover targets in patient tissue samples. Identified targets are validated and characterized for their disease and biological relevance through a suite of wet lab interrogations including expression profiles, epitope mapping, functional screening, phenotypic analyses, and in vitro model systems.

Caris Discovery can be tailored to any therapeutic modality, including antibody-directed therapies, small molecule, targeted protein degradation, synthetic lethal interactions, and neo-antigen directed approaches amongst others.

"Historically, the vast majority of potential drug targets were considered undruggable," said Milan Radovich, Ph.D., Senior Vice President and Chief Precision Medicine Officer of Caris Life Sciences. "With the proliferation of new therapeutic modalities, the universe of targets for cancer medicines has vastly expanded. The combination of Caris ADAPT with our extensive library of real-world clinico-genomics and tissue samples gives our partners exclusive access to difficult-to-find targets within this expanded universe. Ultimately, these targets will lead to novel medicines that transform outcomes for patients with cancer."

Industry Collaborations

Caris Discovery is already gaining traction in the marketplace. In August 2022, Caris entered a multi-year strategic option and license agreement with Xencor, Inc., a clinical-stage biopharmaceutical company, to apply Caris Discovery to identify novel targets for bispecific antibody drug candidates. Just five months later, Caris and Xencor expanded their target discovery collaboration to broaden the scope to additional cancer types with significant unmet need.

"Xencor and Caris share the goal to bring potentially transformational therapies to patients with cancer. We are impressed by their discovery capabilities and are excited to deepen our collaboration with additional tumor histologies," said John Desjarlais, Ph.D., Senior Vice President and Chief Scientific Officer of Xencor. "Caris has built a unique target discovery platform, coupled with deep genomics information, that will enhance our ability to create and evaluate a new generation of XmAb bispecific and multi-specific antibodies, including T cell engagers, NK cell engagers and other modalities."

"Caris is generating a large number of targets across histologies, that once characterized, can be purposefully matched to a therapeutic modality and ideally to a biopharma company that has the expertise and resources to take forward a program into clinical trials," said Brian Lamon, Ph.D., Chief Business Officer of Caris Life Sciences. "With three partnerships announced to date, Caris Discovery is taking a string of pearls-like approach to partnering, mixing and matching joint target discovery collaborations, target out-licensing and target validation, with creative deal structures that align with our partners’ needs and ultimately maximizes the potential for Caris-identified targets to reach the clinic and eradicate tumors."

On January 5, 2023 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and non-alcoholic steatohepatitis (NASH), reported that management will provide an update on its pipeline and strategic priorities for 2023 during the Company’s presentation at the 41st Annual J.P. Morgan Healthcare Conference on January 12, 2023 at 9:00am PT (Press release, Terns Pharmaceuticals, JAN 5, 2023, View Source [SID1234625913]).

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"2022 was a transformative year for Terns as we made important steps forward in our commitment to provide better, new medicines to people battling diseases with significant unmet medical needs. Last year featured an evolution of our pipeline beyond NASH and obesity, as we advanced our oncology pipeline, which carries significant importance to me as an individual recently diagnosed with peritoneal cancer." said Sen Sundaram, chief executive officer of Terns Pharmaceuticals. "We expect 2023 to be an important year for Terns as we assess key inflection points for our clinical programs."

"Prior to our two recent financings, our cash runway supported three key clinical readouts from our three lead programs into 2025. In December 2022, we strengthened our third quarter cash balance sheet with $112 million in equity financing proceeds, resulting in an adjusted cash balance of $293 million.1 These resources are expected to now support operations into 2026, including multiple clinical trials for TERN-501, TERN-701 and/or TERN-601, with our resource allocation to be informed and driven by emerging data," said Mark Vignola, chief financial officer of Terns Pharmaceuticals. "This runway extension does not consider proceeds from potential collaborations in NASH or obesity, which would further solidify our balance sheet to invest more broadly across our development pipeline."

1 $187 million of cash, cash equivalents and marketable securities as of September 30, 2022, together with net offering proceeds of $106 million raised in December 2022

Anticipated 2023 Priorities and Key Milestones

TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML)

Terns expects to initiate a clinical trial for TERN-701 in the United States in the second half of 2023, with potential top-line readouts from initial cohorts in 2024

The decision to initiate a U.S. trial, as well its design, will be informed by data from the ongoing Phase 1 trial conducted by our partner Hansoh in China. The Hansoh trial is a dose-escalation and dose-expansion trial (NCT05367700) evaluating the tolerability, efficacy, and pharmacokinetics of TERN-701 (HS-10382) in approximately 100 patients with CML

Terns expects to publish preclinical data demonstrating TERN-701’s potential in CML and plans to prioritize ongoing publication and presentation of additional supportive data

Due to innovation-limiting price controls for orphan drugs approved for more than one indication that was introduced in the Inflation Reduction Act of 2022 (IRA), Terns does not plan to pursue regulatory approval of TERN-701 for Ph+ acute lymphocytic leukemia (ALL) in the United States, but may pursue approval in countries outside of the United States. Terns continues to evaluate the impact of the IRA across its entire clinical program
"As a peritoneal cancer patient, I have benefitted from treatment with older cancer drugs being studied for new purposes. As such, it pains me to have to forsake my fellow cancer fighters in the United States because of economic policies that stifle medical innovation. I worry that many treatments, such as those that have temporarily extended my own life, could also be abandoned in the United States, and may only wind up being approved in other countries outside the United States," added Mr. Sundaram.

TERN-501: Oral, thyroid hormone receptor-beta (THR-β) agonist for NASH

The Phase 2a DUET trial (NCT05415722), evaluating TERN-501 as a monotherapy and in combination with TERN-101, is on track to complete enrollment in the first quarter of 2023 with top-line data now expected in the third quarter of 2023

Primary endpoint is the relative change from baseline in liver fat content as measured by MRI protein density fat fraction (MRI-PDFF) at Week 12 for TERN-501 monotherapy compared with placebo

Secondary endpoints include assessment of safety and tolerability, pharmacokinetics, changes in MRI-PDFF and MRI corrected T1 (cT1)

DUET is the first trial assessing a THR-β agonist as monotherapy and in combination with an FXR agonist in people with NASH

TERN-501 is a THR-β agonist with high metabolic stability, enhanced liver distribution and greater selectivity for THR-β compared to other THR-β agonists in development

TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity

Terns’ lead GLP-1 receptor agonist program remains on track with the goal of initiating a Phase 1 first-in-human clinical trial in obesity in the second half of 2023 with top-line data expected in 2024

The Company expects to publish preclinical data demonstrating TERN-601’s potential in obesity and plans to prioritize ongoing publication and presentation of additional supportive data

Pre-clinical and Discovery Programs

Terns is conducting pre-clinical in vivo studies evaluating TERN-201, a vascular adhesion protein-1 (VAP-1) inhibitor, co-administered with immune checkpoint inhibitors (e.g., anti-PD1 and anti-CTLA4 antibodies) for solid tumors

Discovery efforts are ongoing for the TERN-800 series of small molecule glucose-dependent insulinotropic polypeptide receptor (GIPR) modulators for obesity, which have the potential for combination with GLP-1 receptor agonists, such as TERN-601
A live audio webcast of the Company’s J.P. Morgan Healthcare Conference presentation will be available on the investor relations page of the Terns Pharmaceuticals website at View Source A replay of the webcast will be archived on Terns’ website for 30 days following the presentation. yhip-

On January 5, 2023 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that the first patient has been dosed in its Phase 1/2 clinical study investigating SRF114, a potential best-in-class, fully human, afucosylated anti-CCR8 antibody, as a monotherapy in patients with advanced solid tumors (Press release, Surface Oncology, JAN 5, 2023, View Source [SID1234625911]).

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"Helping patients fight cancer by depleting intra-tumoral regulatory T cells (Tregs) has been a key goal of many immunotherapy strategies for quite some time. We believe by targeting CCR8, SRF114 is well suited to explore the promise of this approach," said Alison O’Neill, M.D., chief medical officer of Surface Oncology. "We selected our SRF114 antibody based on its highly specific binding properties to human CCR8 exclusively, which we believe positions it as a potential best-in-class anti-CCR8 antibody for the treatment of advanced solid tumors."

The Phase 1/2 trial is an open-label, first-in-human, dose-escalation and expansion study of SRF114 as a monotherapy in patients with advanced solid tumors that will be conducted in two parts. Part A, the monotherapy dose-escalation portion of the study, will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of SRF114 in patients with advanced solid tumors. Once Part A is completed, Part B will evaluate SRF114 in up to 40 patients with head and neck squamous cell carcinoma (HNSCC) as a monotherapy. Surface expects to provide initial clinical data in 2024.

About SRF114

SRF114 is a fully human, afucosylated anti-CCR8 antibody designed to preferentially deplete CCR8+ Treg cells within the tumor microenvironment. In pre-clinical studies, Surface Oncology has shown that SRF114 induces antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) pathways to deplete intratumoral Treg cells. In addition, SRF114 reduced tumor growth in murine models. These findings support the advancement of SRF114 as a therapeutic candidate that holds the potential to drive anti-tumor immunity in patients.