On May 26, 2022 Chiome Bioscience Inc. reported joint research agreement with Kidswell Bio Corporation (Press release, Chiome Bioscience, MAY 26, 2022, View Source [SID1234625711]). The collaborative research makes us join their ongoing research project to develop therapeutic antibody for cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Our mission is to shine the light on unmet medical needs through our research project of drug discovery and development. This collaborative research will expect to merge our research functions and experiences with novel antibody drug discovery project. We will continue to discuss the extended collaboration scheme with Kidswell Bio in case our joint research make the progress pushing the project up to the therapeutic drug development stage.

On May 26, 2022 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported the publication of an abstract at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Onconova, MAY 26, 2022, View Source [SID1234615195]). Featured in the abstract are preclinical data from in vitro and cell-based assays that demonstrate how narazaciclib’s inhibitory profile differentiates it from the FDA-approved CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Key data and conclusions from the abstract include:

Narazaciclib, abemaciclib, palbociclib, and ribociclib each have strong affinity for CDK4/cyclin D1, with Kd values of 0.18 nM, 0.08 nM, 0.75 nM, and 1.3 nM, respectively.

Narazaciclib and abemaciclib have similar affinities against CDK family members, including nM activity against CDK2/cyclin A, which may play a role in resistance to palbociclib and ribociclib.

Narazaciclib’s inhibitory activity against GSK3β, a kinase whose inhibition putatively causes tolerability issues related to diarrhea, is ~29 times less than that of abemaciclib.

Cellular kinase assays showed narazaciclib’s highest inhibitory activity to be against CDK4/6, CSF1R, (supports pro-tumor immune suppression), and NUAK1/ARK 5 (associated with poor prognosis in multiple cancers and implicated in cancer cell migration, invasion, and metastasis).

Cellular Thermal Shift Assay (CETSA) and integrative Inferred Kinase Activity (INKA) analysis showed that narazaciclib is associated with and modulated unique signaling pathways resulting in specific deregulated phosphorylation patterns when compared to palbociclib treated cells.
Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova and co-author of the abstract, commented, "Though revolutionary and commercially successful, currently available CDK4/6 inhibitors are limited by tolerability and safety issues as well as the unfortunate reality of primary and acquired drug resistance. This creates a pressing unmet need for novel agents that may overcome these shortcomings and provide patients with durable clinical benefit. Narazaciclib’s decreased affinity for targets associated with poor tolerability, together with its increased inhibitory activity against kinases implicated in metastasis, cancer cell survival, immune suppression, and drug resistance, suggests it may address this need. We continue to explore this hypothesis in narazaciclib’s clinical program and remain on track to establish a recommended Phase 2 dose by the end of the year."

A copy of the abstract, titled, "Narazaciclib’s kinase inhibitory activity is differentiated from approved CDK4/6 inhibitors in preclinical models," is available on the ASCO (Free ASCO Whitepaper) Annual Meeting website.

On May 26, 2022 Checkmate Pharmaceuticals, Inc. (NASDAQ: CMPI) ("Checkmate"), a clinical stage biotechnology company focused on developing its proprietary technology to harness the power of the immune system to combat cancer, reported the University of Iowa Holden Comprehensive Cancer Center’s presentation of preliminary data from an investigator-sponsored phase 1/2 trial evaluating vidutolimod, a first-in-class, immunostimulatory, noninfectious virus-like particle (VLP) containing a CpG-A Toll-like receptor 9 (TLR9) agonist (Press release, Checkmate Pharmaceuticals, MAY 26, 2022, View Source [SID1234615194]). The early phase trial is investigating intratumoral vidutolimod therapy in combination with intravenous pembrolizumab in patients with relapsed lymphoma. The objective of this study is to determine the dose of vidutolimod that, in combination with pembrolizumab, has optimal clinical efficacy and acceptable toxicity in patients with relapsed lymphoma who have failed at least one line of therapy. In addition to the funding provided by Checkmate, the ongoing study is supported by NCI grant P50 CA97274 to the University of Iowa/Mayo Clinic (UI/MC) Lymphoma SPORE (specialized program of research excellence).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Preliminary results from an early-phase trial of in situ immunization of lymphoma with a virus-like particle containing a TLR9 agonist combined with anti–PD-1 therapy (Abstract #: 2639: NCT03983668)

During the 2022 ASCO (Free ASCO Whitepaper) Developmental Therapeutics—Immunotherapy Poster Session on Sunday, June 5 at 9:00am ET, Umar Farooq, M.D., Clinical Associate Professor of Internal Medicine at University of Iowa Hospitals & Clinics, principal investigator, and study sponsor, will present preliminary safety, response and translational laboratory data from 7 enrolled patients with relapsed lymphoma.
Key highlights from the presentation include:

Preliminary results suggest that in situ immunization with vidutolimod plus systemic pembrolizumab had clinical activity in a variety of lymphomas in 5 of 7 patients studied
No significant adverse effects (AEs) were reported after the 4-hour observation period other than mild headache or fatigue lasting only through day 1
Consistent with preclinical data, generation of anti-Qβ antibodies after the initial subcutaneous (SC) vidutolimod dose correlated with response to study treatment; further evaluation in additional patients is needed to confirm these initial observations
Additional evaluation of complex interactions between cells in the tumor microenvironment in response to vidutolimod will be needed to understand these findings
Study enrollment is ongoing and given the common use of B cell depleting therapies for the treatment of certain lymphomas, the study was modified to require generation of anti-Qβ antibodies after the initial SC dose of vidutolimod before patients receive IT therapy.

"Our understanding of the immune and therapeutic responses to intratumoral vidutolimod with checkpoint inhibitors continues to grow stronger based on these data," said Art Krieg, M.D., Founder and Chief Scientific Officer of Checkmate. "These initial observations provide valuable insights into the mechanism of action of vidutolimod and reinforce earlier preclinical data from the Iowa team that suggest the activity of vidutolimod requires the generation of anti-Qβ antibodies. We look forward to the continued investigation of vidutolimod in combination with immune checkpoint inhibitors to improve available treatment options for people with lymphoma and other difficult to treat cancers."

On May 26, 2022 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported interim safety and efficacy data from the ongoing dose escalation and expansion study evaluating HPN328, Harpoon’s half-life extended TriTAC targeting delta-like canonical Notch ligand 3 (DLL3), for the treatment of SCLC and other neuroendocrine cancers (Press release, Harpoon Therapeutics, MAY 26, 2022, View Source [SID1234615193]). The first scientific presentation of these interim data will be featured in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2022, taking place in Chicago from June 3-7.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The encouraging interim results, as of the data cut-off date of April 21, 2022, showed that HPN328 demonstrated anti-tumor activity and a favorable safety profile in patients with SCLC, neuroendocrine prostate cancer and other neuroendocrine cancers. Seven of 18 patients (39%) had a decrease in sum of target lesion diameters, with 3 of 11 patients (27%) with SCLC across all dose cohorts experiencing a greater than 30% decrease in sum of target lesion diameters. Additionally, 4 of 6 patients (67%) with SCLC treated at greater than or equal to 1.215mg/week experienced a decrease in sum of target lesion diameters. To date, there have been no dose-limiting toxicities observed and no discontinuations due to adverse events. Grade 1-2 CRS occurred in 22% of patients. No grade 3 or higher CRS or any immune effector cell associated neurotoxicity syndrome (ICANS) events have been observed.

"DLL3 is expressed on the surface of tumor cells in more than 70% of small cell carcinomas, including small cell lung cancer, neuroendocrine prostate cancer, and other small cell neuroendocrine cancers, and HPN328 is specifically engineered to hit this target," said Himisha Beltran, M.D., of Dana-Farber Cancer Institute, Boston, a Principal Investigator in this study. "The encouraging single-agent clinical activity observed to date in patients that have received multiple prior lines of therapy, combined with the favorable safety profile, suggest the investigational T cell engager HPN328 may offer meaningful clinical benefits as a monotherapy for patients expressing DLL3. I look forward to the clinical results from further investigations with this promising drug candidate."

To date, study investigators have observed 1 confirmed partial response with a 53% decrease in sum of target lesion diameters at week 10 in a patient with SCLC who previously achieved a best overall response of stable disease on platinum-based chemo-immunotherapy. Another SCLC patient treated with 3 prior lines of therapy achieved a 65% decrease in sum of target lesion diameters with deepening of target lesion response, with treatment ongoing beyond six months. There were 6 instances of patients with best overall response of stable disease (4 SCLC, 1 neuroendocrine prostate cancer, and 1 thymic atypical carcinoid).

"We are pleased to share our continued progress with the HPN328 anti-DLL3 T cell engager clinical program and these interim data in a peer-reviewed setting, providing further clinical validation for our TriTAC technology in solid tumors," said Julie Eastland, President and CEO of Harpoon Therapeutics. "Given the clinical activity and acceptable tolerability profile observed to date, we look forward to continuing dose escalation, with the goal of identifying a dose for expansion studies by the end of the year, as we further explore the full potential of HPN328 as both a single agent and in future combination studies with atezolizumab to help patients with cancer."

Details of the ASCO (Free ASCO Whitepaper) poster presentation are as follows:

Title: Interim results of an ongoing phase 1/2a study of HPN328, a tri-specific, half-life extended, DLL3-targeting, T cell engager, in patients with small cell lung cancer and other neuroendocrine cancers
Abstract/Poster: 8566/193
Session Title: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Session Date and Time: Monday, June 6, 8:00 a.m. to 11:00 a.m. CT

About HPN328

HPN328, a Tri-specific T cell Activating Construct (TriTAC), is being evaluated as monotherapy in an ongoing open-label, multicenter two-part study to assess the safety, tolerability and pharmacokinetics in patients with advanced cancers associated with expression of DLL3. Part 1 of the study is designed to determine dosage(s) for further evaluation in expansion cohorts during Part 2.

In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to HPN328 for the treatment of SCLC.

For additional information on the HPN328 clinical study, please go to ClinicalTrials.gov and use Identifier NCT04471727.

On May 26, 2022 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of injectable biologics to selectively engage and modulate targeted T cells directly within the patient’s body, reported it will give a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held in-person June 3–7 at the McCormick Place Convention Center in Chicago, Illinois and virtually (Press release, Cue Biopharma, MAY 26, 2022, View Source [SID1234615192]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster presents interim clinical data supporting the tolerability and antitumor activity of Cue Biopharma’s lead interleukin 2 (IL-2)-based CUE-100 series therapeutic, CUE-101, both as a monotherapy and in combination with pembrolizumab (KEYTRUDA) for the treatment of patients with recurrent/metastatic HPV16+ head and neck cancer.

Presentation Details:
Title: A Phase 1 dose-escalation and expansion study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, given alone and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer
Abstract #: 6045
Presenter: Dr. Christine Chung, M.D., Chair, Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa FL
Date: Monday, June 6, 2022, 1:15–4:15 p.m. CDT

The poster will be available in the Investor & Media section of the Company’s website at www.cuebiopharma.com under Scientific Publications and Presentations, following the presentation.

About ASCO (Free ASCO Whitepaper)
Founded in 1964, the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), Inc. (ASCO) (Free ASCO Whitepaper) is committed to making a world of difference in cancer care. As the world’s leading organization of its kind, ASCO (Free ASCO Whitepaper) represents nearly 45,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of the highest-quality patient care, ASCO (Free ASCO Whitepaper) works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. More than 40,000 oncology professionals from around the world convene at the ASCO (Free ASCO Whitepaper) Annual Meeting to share new clinical cancer advances in every area of cancer research, gain real-time insights from world-renown faculty, and connect with one of the largest, most diverse audiences in global oncology.

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing the potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.

About Immuno-STAT
The company’s Immuno-STAT (Selective Targeting and Alteration of T cells) biologics are designed for targeted modulation of disease-associated T cells in the areas of immuno-oncology and autoimmune disease. Each of our biologic drugs is designed using our proprietary scaffold comprising: 1) a pMHC to provide selectivity through interaction with the T cell receptor (TCR), and 2) a unique co-stimulatory signaling molecule to modulate the activity of the target T cells. The simultaneous engagement of co-regulatory molecules and pMHC binding mimics the signals delivered by antigen presenting cells (APCs) to T cells during a natural immune response. This design enables Immuno-STAT biologics to engage with the T cell population of interest, resulting in selective T cell modulation. Because our drug candidates are delivered directly in the patient’s body (in vivo), they are fundamentally different from other T cell therapeutic approaches that require the patients’ T cells to be extracted, modified outside the body (ex vivo), and reinfused.