On December 14, 2021 Cellworks Group, Inc., a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology, reported results from the myCare-023 clinical trial, which found that the Cellworks Biosimulation Platform with its Therapy Response Index (TRI) reliably predicts complete response (CR) and overall survival (OS) for individual Acute Myeloid Leukemia (AML) patients beyond physician prescribed treatment (Press release, Cellworks, DEC 14, 2021, View Source [SID1234597124]). The myCare-023 study also showed that the Cellworks platform can provide personalized, molecular-based alternate treatment options for AML patients who are predicted to be non-responders to standard care therapies.

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"Except for a few targeted therapies, genomic assessment has offered little guidance on treatment for AML patients," said Dr. Guido Marcucci, MD, Chair and Professor, Department of Hematologic Malignancies Translational Science; Director, Gehr Family Center for Leukemia Research, and Chief of Leukemia Division within the Department of Hematology & Hematopoietic Cell Transplantation, City of Hope; and Principal Investigator for the myCare-023 clinical trial. "This study shows that the Cellworks Biosimulation Platform has the potential to improve treatment guidance by utilizing a comprehensive molecular genomic network to model each patient’s unique cancer and predict how they will respond to specific treatments. Through this personalized therapy biosimulation approach, we can individualize treatment selection and improve patient outcomes."

The results from the myCare-023 clinical trial were featured as an oral presentation given by Dr. Scott Howard, MD, MSc, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on December 13, 2021 in Atlanta, Georgia and available online in the ASH (Free ASH Whitepaper) Meeting Library as Abstract 689.

"Complete remission and cure rates for AML have significant room for improvement," said Dr. Scott Howard, MD, MSc, University of Tennessee Health Science Center. "Comprehensive molecular profiling shows us that AML is a complex and heterogeneous disease network which impacts the efficacy of individual chemotherapeutics differently in individual patients. By using the Cellworks personalized therapy biosimulation platform to predict the impact of an individual patient’s aberrations and copy number alternations on therapy response, we can address the heterogeneous nature of AML and improve complete remission and cure rates."

The Cellworks Biosimulation Platform simulates how a patient’s personalized genomic disease model will respond to therapies prior to treatment and identifies novel drug combinations for treatment-refractory patients. The platform is powered by the groundbreaking Cellworks Computational Omics Biology Model (CBM), a network of 4,000+ human genes, 30,000+ molecular species and 100+ signaling pathways. As part of the biosimulation process, personalized disease models are created for each patient using their cytogenetic and molecular data as input to the Cellworks CBM. The Cellworks platform analyzes the impact of specific therapies on the patient’s personalized disease model and generates a Singula biosimulation report with Therapy Response Index (TRI) Scores that predict the efficacy of specific chemotherapies.

"The use of genomics to guide therapy for AML patients has generally been restricted to a single-gene approach, which rarely has sufficient predictive power to be clinically useful," said Dr. Guido Marcucci, MD. "However, comprehensive DNA sequencing used with Cellworks personalized therapy biosimulation can guide optimal treatment selection for individual patients, help patients avoid ineffective therapies and improve patient outcomes."

Clinical Study: myCare-023

ASH Abstract 689: Therapy biosimulation using the Cellworks Computational Omics Biology Model (CBM) is predictive of individual AML patient probability of clinical response and overall survival.

Methods

Cytogenetic and molecular data obtained from clinical trials including AMLSG 07-04, Beat AML, TCGA and PubMed publications was used to create a personalized in silico models of each patient’s AML. The impact of specific AML therapies on each patient’s disease model was biosimulated to determine a treatment efficacy score by estimating the effect of chemotherapy on the cell growth score, a composite of cell proliferation, viability, apoptosis, metastasis, DNA damage and other cancer hallmarks. The mechanism of action of each therapy was mapped to each patient’s genome and biological consequences determined response.

Results

In this study, specific leukemia therapies generated a variable likelihood of benefit for individual patients. The Cellworks TRI score, scaled from 0 to 100, predicted complete response with a likelihood ratio χ12 = 52.54, p < 0.0001. The Cellworks Biosimulation Platform was able to predict treatment benefit or failure better than physician prescribed treatment alone (likelihood ratio χ12 = 14.86, p < 0.0001). The use of therapy biosimulation to select therapy is estimated to increase odds of complete response by 19% per every 25 units of the TRI score.

TRI scores were also a significant predictor of overall survival (likelihood ratio χ12 = 80.41, p < 0.0001) and provides predictive information above and beyond physician prescribed treatment alone (likelihood ratio χ12 = 58.70, p < 0.0001). Inclusion of the Cellworks biosimulation is estimated to reduce the hazard ratio for death above and beyond physician prescribed treatment by 16% per every 25 units of the TRI score.

In addition, predictiveness curves suggest that approximately 25% of de novo AML patients had low probability of complete response resulting in lower overall survival and could benefit substantially from inclusion of therapies and combinations identified by Cellworks biosimulation into frontline management.

Conclusions

This study found that Cellworks TRI predicts complete response and overall survival beyond physician prescribed treatment alone and the Cellworks platform provides individualized, molecular-based alternate treatment options for patients predicted to be non-responders to standard care therapies.

On December 14, 2021 Secura Bio, Inc. (Secura Bio) – (www.securabio.com), an integrated pharmaceutical company dedicated to the worldwide development and commercialization of impactful oncology therapies, reported that new data for the treatment of relapsed or refractory(r/r) PTCL patients with COPIKTRA were presented at the 63rd annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta, Georgia (Press release, Secura Bio, DEC 14, 2021, View Source [SID1234597159]).

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Jonathan Brammer M.D. of The Ohio State University James Comprehensive Cancer Center presented the interim analysis of the phase 2 PRIMO trial of r/r PTCL patients treated with single-agent COPIKTRA 75mg BID for the first two months followed by 25mg BID until progression or unacceptable toxicity. 78 of a planned 125 patients were included in this analysis with a minimum follow-up of 6 months. The trial is ongoing, with completion expected in 2022.

The interim results include an ORR by IRC assessment of 50% (39/78 pts) and a CR of 32.1% (25/78) with a median duration of response of 233 days (range, 1-420+). Patients had a median of 3 (range, 1-7) prior therapeutic regimens and included the following PTCL subtypes: PTCL NOS (53.8%), ALCL (14.1%), AITL (26.0%) and Other (0.5%). 18% of patients remain on therapy, 47.4% discontinued due to PD, 6.4% discontinued for stem cell transplant, and 19.2% discontinued due to unacceptable toxicity.

Overall, the safety profile was consistent with previous studies; in this analysis the most frequent > Grade 3 adverse events seen were neutropenia (38.5%), ALT/AST increased (24.4%/ 21.8%), rash (7.7%), lymphocyte count decreased (7.7%), and sepsis (6.4%). ALT and/or AST elevations were the most common AEs leading to treatment discontinuations (N=12, 15.4%).

"Patients with r/r PTCL usually relapse quickly and have limited treatment options, and the data from the PRIMO trial show very promising activity and even a remarkable number of complete responses. Importantly, these responses are better than current standard of care options" said Dr. Brammer.

"We are encouraged to see such robust responses in a significant number of patients who are suffering with these aggressive forms of lymphoma" said David Cohan M.D., Chief Medical Officer at Secura Bio. "We will continue to develop COPIKTRA for the treatment of the r/r population, and we have also expanded our clinical research program to include earlier lines of therapy for various T-cell lymphomas."

The original abstract published for ASH (Free ASH Whitepaper) can be viewed by clicking HERE.

About COPIKTRA (duvelisib)

COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first United States FDA approved dual inhibitor of PI3K-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant cells. PI3K signaling may lead to the proliferation of malignant cells and is thought to play a role in the formation and maintenance of a supportive tumor microenvironment. COPIKTRA is indicated in the United States for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies. COPIKTRA is also being developed for the treatment of peripheral T-cell lymphoma (PTCL), for which it has received Fast Track designation in the United States. COPIKTRA is being investigated in combination with other agents across several types of solid and hematologic malignancies, through investigator-sponsored studies. For more information on COPIKTRA, please visit www.COPIKTRA.com. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

IMPORTANT SAFETY INFORMATION ABOUT COPIKTRA

WARNING: FATAL AND SERIOUS TOXICITIES: INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS, and PNEUMONITIS

See full prescribing information for complete boxed warning

Fatal and/or serious infections occurred in 31% (4% fatal) of COPIKTRA-treated patients. Monitor for signs and symptoms of infection. Withhold COPIKTRA if infection is suspected.
Fatal and/or serious diarrhea or colitis occurred in 18% (<1% fatal) of COPIKTRA-treated patients. Monitor for the development of severe diarrhea or colitis. Withhold COPIKTRA.
Fatal and/or serious cutaneous reactions occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Withhold COPIKTRA.
Fatal and/or serious pneumonitis occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Monitor for pulmonary symptoms and interstitial infiltrates. Withhold COPIKTRA.
INDICATIONS AND USAGE

COPIKTRA is a kinase inhibitor indicated for the treatment of adult patients with:

Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies.

WARNINGS AND PRECAUTIONS

Hepatotoxicity: Monitor hepatic function.
Neutropenia: Monitor blood counts.
Embryo-Fetal toxicity: COPIKTRA can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS

The most common adverse reactions (≥20%) are diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.

DRUG INTERACTIONS

CYP3A inducers: Avoid co-administration with strong CYP3A inducers.
CYP3A inhibitors: Monitor for COPIKTRA toxicities when co-administered with strong or moderate CYP3A inhibitors. Reduce COPIKTRA dose to 15 mg twice daily when co-administered with strong CYP3A4 inhibitors.
CYP3A substrates: Monitor for signs of toxicities when co-administering COPIKTRA with sensitive CYP3A substrates.
USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed.

On December 14, 2021 HiberCell, a clinical-stage biotechnology company developing therapeutics to address therapeutic resistance, cancer relapse and metastasis, reported a clinical trial collaboration with Merck, known as MSD outside of the United States and Canada (Press release, HiberCell, DEC 14, 2021, View Source;utm_medium=rss&utm_campaign=hibercell-to-collaborate-with-merck-on-phase-2-clinical-trial-of-odetiglucan-in-combination-with-keytruda-pembrolizumab-in-patients-with-metastatic-breast-cancer [SID1234597060]). This metastatic breast cancer clinical trial evaluates KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with HiberCell’s odetiglucan (Imprime PGG), a Dectin-1, pattern recognition receptor agonist.

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Odetiglucan, a novel intravenously-administered innate immune activator, has been previously investigated in combination with pembrolizumab in immune checkpoint inhibitor-naive TNBC, as well as non-small cell lung carcinoma in combination with other immune checkpoint inhibitors, anti-angiogenic antibodies, and tumor-targeting antibodies. Under this collaboration with Merck, the phase 2 single arm, open-label clinical trial is anticipated to enroll up to 50 patients with metastatic breast cancer who have progressed through prior hormone therapy with at least one CDK4/6 inhibitor in sites across the United States. Merck will provide KEYTRUDA for the planned clinical trials.

"We are pleased to continue the important work that we began five years ago, with a focus on improving outcomes for cancer patients who suffer from treatment-mediated resistance," said Alan Rigby, Ph.D., chief executive officer at HiberCell. "This clinical trial is expected to build upon encouraging clinical and translational data from our prior collaborative studies with the team at Merck, which investigated odetiglucan in combination with pembrolizumab in metastatic TNBC. The data-driven decision to establish a new clinical trial represents an expansion of our odetiglucan clinical development program and highlights our continued priority of combining odetiglucan with other therapies in an effort to develop new treatment options."

For more information about HiberCell’s odetiglucan, visit the company’s website at View Source

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About Odetiglucan
Odetiglucan is a Dectin-1, pattern recognition receptor agonist that drives a coordinated innate and adaptive anti-cancer immune cell response in metastatic cancers including TNBC, melanoma, and non-small cell lung carcinoma. Phase 2 clinical studies of odetiglucan in combination with immune checkpoint inhibitors have demonstrated mechanistic proof-of-concept data including the activation of innate and adaptive immunity that has resulted in clinical benefit for patients.

On December 14, 2021 OnKure, Inc., a clinical-stage biopharmaceutical company discovering and developing the next generation of oncology precision medicines, reported positive topline results from the first-in-human Phase 1 trial of OKI-179, the Company’s oral Class 1 histone deacetylase (HDAC) inhibitor (Press release, OnKure, DEC 14, 2021, View Source;utm_medium=rss&utm_campaign=onkure-therapeutics-announces-positive-topline-first-in-human-phase-1-results-for-oki-179 [SID1234597085]).

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The first-in-human Phase 1 dose-finding study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of escalating oral doses of OKI-179 in cancer patients. OKI-179 was shown to be safe and generally well-tolerated as a single agent using intermittent dosing schedules of either 4 days on/3 days off or 5 days on/2 days off for 21 days. The most common adverse events were nausea, fatigue and anemia. Nausea was manageable with antiemetics.

At doses of 120 mg and above, PK/PD data demonstrated robust target engagement, with exposures that were above the pharmacologically active concentrations observed in multiple preclinical, solid tumor models of RAS pathway mutated cancers. Results from this study indicate that 450 mg and 300 mg are the maximum tolerated doses for the 4 days on/3 days off and 5 days on/2 days off schedules, respectively.

"HDAC inhibitors have shown great promise, however they have little success treating solid tumors due to poor tolerability. We are extremely encouraged by these Phase 1 results and we believe OKI-179 can overcome the historic limitations, having demonstrated high levels of target engagement at two well-tolerated dosing schedules," said Tony Piscopio, Ph.D., Co-Founder, President and Chief Executive Officer of OnKure. "We look forward to investigating our promising selective HDAC inhibitor as a potential treatment for a wide range of solid malignancies."

"We are excited by the results of our first-in-human trial of OKI-179 that demonstrate a best-in-class selectivity and tolerability profile in an oral HDAC inhibitor," said Jennifer Diamond, M.D., Chief Medical Officer of OnKure. "Class 1 HDAC inhibitors have shown chemical synthetic lethality with RAS pathway inhibitors in cell-line and patient-derived tumor models that harbor mutations in the RAS pathway, driving increased cell death and tumor regressions."

Dr. Diamond continued: "With approximately 25-35% of all cancers having mutations in the RAS pathway, OKI-179 has the potential to change the treatment paradigm for many tumor types, potentially becoming a backbone therapy for all RAS mutated cancers in combination with a RAS-pathway inhibitor."

Based on these favorable results, the Company expects to initiate a Phase 1b/2 trial of OKI-179 in combination with binimetinib in patients with NRAS mutant melanoma where checkpoint inhibitor therapy has failed in the first half of 2022. This trial will initially evaluate safety, PK and PD of the combination and establish a recommended Phase 2 dose before initiating the open-label Phase 2 portion of the study.

About OKI-179
OKI-179 is a novel, oral Class 1 histone deacetylase (HDAC) inhibitor for the potential treatment of a wide range of solid and hematological malignancies. HDAC inhibitors have shown great promise in preclinical models, however they have had little success treating solid tumors, often due to poor tolerability, inappropriate dosing regimens, poorly conceived combinations, and a lack of stratifying biomarkers. OKI-179 is designed to have improved potency, selectivity, tolerability, as well as easy combinability to overcome the historic limitations of other HDAC inhibitors. OnKure is currently planning to conduct a Phase 1b/2 trial of OKI-179 in combination with binimetinib in patients with NRAS mutant melanoma in 2022.

On December 14, 2021 AnHeart Therapeutics ("AnHeart"), a clinical-stage global biopharmaceutical group company committed to developing novel precision oncology therapies, reported the completion of a $61 million oversubscribed Series B financing round led by new investor Octagon Capital, with participation from Innovent Biologics, Cenova, Laurion Capital, and Sage Partners (Press release, AnHeart Therapeutics, DEC 14, 2021, View Source [SID1234597125]). The Company has raised a total of $100 million in gross proceeds from private financings since its founding in December 2018.

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The proceeds from the Series B financing will be used to advance the clinical development of AnHeart’s lead asset, taletrectinib, a next-generation ROS1 inhibitor currently in Phase 2 trials in non-small cell lung cancer (NSCLC), and support the continued expansion of its pipeline of precision next-generation oncology therapeutics.

ROS1 oncogenic fusions are observed in approximately 1-2% of or about 20,000 NSCLC patients each year worldwide. ROS1 fusions are also observed in several other cancers such as cholangiocarcinoma, glioblastoma, ovarian, gastric, and colorectal cancers. NTRK fusions are oncogenic driver across multiple advanced solid tumors and observed in more than 90% in very rare cancers such as secretory breast carcinoma, mammary analogue secretory carcinoma of salivary gland and infantile fibrosarcoma, 12.1~14.5% of papillary thyroid cancer and 10.3% of non-brainstem high grade glioma. Incidence of NTRK fusions is below 5% in more common cancers such as lung, breast, melanoma, and colon cancer.

Taletrectinib is a potent, novel, highly selective, next-generation ROS1/NTRK inhibitor for solid tumors with ROS1 fusion or NTRK fusion mutations. It can overcome crizotinib resistance and cross the blood-brain barrier. There is currently no FDA approved drug targeting crizotinib resistance mutations. Taletrectinib is currently in China TRUST trial (Taletrectinib ROS1 LUng STudy, NCT04395677), global TRUST II trial (NCT04919811) and the basket trial in NTRK fusion positive solid tumors (NCT04617054). Impressive interim data of the TRUST Phase 2 trial for NSCLC have been published at ASCO (Free ASCO Whitepaper) and CSCO earlier this year.

"AnHeart is delighted to partner with this group of top-tier, leading healthcare investors to advance development of our pipeline of precision oncology therapeutics. We have made tremendous progress since we founded AnHeart in 2018," Junyuan (Jerry) Wang, Ph.D., Co-Founder and Chief Executive Officer of AnHeart Therapeutics. "This financing reflects strong support for our platform, people, and comprehensive development strategy."

"This strong investment group, comprised of both healthcare specialist funds and a leading biopharma company allows us to accelerate development of our unique pipeline of targeted therapies," said Lihua Zheng, J.D., Ph.D., Co-Founder and Chief Business Officer of AnHeart Therapeutics. "The funding will also allow us to continue expanding our team of world-class scientists and researchers focused on bringing game-changing cancer therapeutics to improve patients’ lives."

"We were attracted to AnHeart by the excellent science, experienced management team and broad pipeline of targeted small molecule therapeutics," said Dr. Ting Jia, "TJ", Ph.D., Founder, Octagon Capital, a New York-based healthcare specialist fund active in both private and public markets. "AnHeart’s lead asset taletrectinib is a promising potential new therapeutic in ROS1 fusion-positive lung cancer patients, with impressive preliminary Phase 2 clinical data reported at ASCO (Free ASCO Whitepaper) and CSCO this year. In addition, we see a tremendous opportunity for AnHeart’s pipeline to produce novel, targeted therapies to address significant unmet medical needs across a broad range of difficult-to-treat cancers."