On September 21, 2020 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported updated clinical data from the pivotal trial of envafolimab in MSI-H/dMMR cancer patients that were recently presented by the Company’s corporate partners, 3D Medicines and Alphamab Oncology (Press release, Tracon Pharmaceuticals, SEP 21, 2020, View Source [SID1234565439]).

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In a presentation highlighting updated clinical results at the Chinese Society of Clinical Oncology (CSCO) 2020 Virtual Scientific Program entitled, "Subcutaneous Injection of PD-L1 Antibody Envafolimab (KN035) in Advanced Tumors with Mismatch-Repair Deficiency," single agent envafolimab was shown to have a 32% confirmed objective response rate (ORR) by central radiographic review of 41 patients with MSI-H/dMMR colorectal cancer (CRC) who failed a fluoropyrimidine, oxaliplatin and irinotecan, and had at least two on-study tumor assessments. Duration of response (DOR) was greater than or equal to 12 months in 75% of patients and overall survival (OS) was greater than or equal to 12 months in 65% of patients. The ORR in the overall population (N=103) was 43%, DOR was greater than or equal to 12 months in 92% of patients and OS was greater than or equal to 12 months in 75% of patients. Envafolimab demonstrated good tolerability and safety and there continued to be no infusion-related reactions.

Earlier data from this trial were presented by 3D Medicines and Alphamab Oncology at ASCO (Free ASCO Whitepaper) 2020, in a presentation entitled, "Envafolimab (KN035) in Advanced Tumors with Mismatch-Repair Deficiency," at which time single agent envafolimab was shown to have a 28% confirmed ORR by central radiographic review in 39 patients with MSI-H/dMMR CRC who failed a fluoropyrimidine, oxaliplatin and irinotecan, and had at least two on-study tumor assessments. The trial enrolled 103 patients with MSI-H CRC, GC or with dMMR in other advanced solid tumors at clinical sites in China, in an open label format with efficacy endpoints, including the primary endpoint of confirmed ORR determined by independent central review. MSI-H/dMMR status was assessed centrally for CRC and GC and locally for other tumors.

The confirmed ORR in MSI-H/dMMR colorectal cancer patients treated with envafolimab who failed a fluoropyrimidine, oxaliplatin and irinotecan reported at CSCO 2020 of 32% is similar to the 28% confirmed ORR reported in the Opdivo package insert in MSI-H/dMMR colorectal cancer patients who failed a fluoropyrimidine, oxaliplatin, and irinotecan, and the 27.9% confirmed ORR reported for Keytruda in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin and irinotecan seen in cohort A of the pivotal KEYNOTE-164 trial.

"The CSCO 2020 data provide further clinical evidence that envafolimab’s activity is similar to that of Opdivo and Keytruda in MSI-H/dMMR cancer. Also impressive is the durability of response at 12 months," said James Freddo, M.D., TRACON Chief Medical Officer. "Given the 4% ORR reported in the pivotal study of Votrient, the only approved therapy for refractory UPS and MFS, and the demonstrated efficacy of immune checkpoint inhibitors in these populations, we believe the clinical results of our ENVASARC pivotal trial, if positive, could position envafolimab as a transformative new standard of care for sarcoma patients. Moreover, the elimination of PD-L1 associated infusion-related reactions observed to date and the convenience provided by envafolimab as the only subcutaneously administered PD-L1 inhibitor currently being studied in registrational trials, could provide significant benefits for clinicians and their patients."

About ENVASARC

Key elements for the planned ENVASARC pivotal trial include:

Multi-center, open-label, randomized, non-comparative, parallel cohort study at approximately 25 top cancer centers in the United States.
Eligible patients will have undifferentiated pleomorphic sarcoma (UPS) or myxofibrosarcoma (MFS) and received one or two prior cancer therapies, but no prior immune checkpoint inhibitor therapy.
Planned total enrollment of 160 patients, with 80 patients enrolled into cohort A of treatment with single agent envafolimab and 80 patients enrolled in cohort B of treatment with envafolimab and Yervoy.
Primary endpoint of confirmed ORR with duration of response a key secondary endpoint.
Open-label format with blinded independent central review of efficacy endpoint data.
About Envafolimab

Envafolimab (KN035), a novel, single-domain antibody against PD-L1, is the first subcutaneously administered PD-(L)1 inhibitor to be studied in registrational trials. Envafolimab is currently dosing in a Phase 2 registration trial as a single agent in MSI-H/dMMR advanced solid tumor patients and a Phase 3 registration trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China. 3D Medicines and Alphamab Oncology, TRACON’s corporate partners for this program, plan to submit a BLA to the NMPA in China for envafolimab in 2020 based on the ORR in MSI-H/dMMR advanced solid tumor patients. The confirmed ORR in MSI-H/dMMR colorectal cancer patients treated with envafolimab who failed a fluoropyrimidine, oxaliplatin and irinotecan reported at CSCO 2020 was 32%, which was similar to the 28% confirmed ORR reported in the Opdivo package insert in MSI-H/dMMR colorectal cancer patients who failed a fluoropyrimidine, oxaliplatin, and irinotecan and the 27.9% confirmed ORR reported for Keytruda in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin and irinotecan in cohort A of KEYNOTE-164.

On September 21, 2020 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the presentation of interim clinical data from its ongoing Phase 1 clinical trial evaluating TK216, an investigational, potentially first-in-class, targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins, in patients with relapsed or refractory Ewing sarcoma (Press release, Oncternal Therapeutics, SEP 21, 2020, View Source [SID1234565438]). Joseph A Ludwig, M.D., Associate Professor in the Department of Sarcoma Medical Oncology at The University of Texas MD Anderson Cancer Center, presented the results in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 on September 20, 2020.

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"I am very encouraged by the complete responses to TK216 in these two heavily pre-treated patients with Ewing sarcoma," said Dr. Ludwig. "Advanced, refractory Ewing sarcoma is a serious and devastating condition, with no approved therapies, and novel therapeutic approaches are desperately needed. These positive interim clinical results suggest that TK216 holds promise for patients with Ewing sarcoma with no alternatives and poor prognoses."

This ongoing clinical trial is a first-in-human, multicenter Phase 1 study of TK216 in patients with relapsed or refractory Ewing sarcoma. Trial objectives include the evaluation of safety, tolerability, pharmacokinetics, and tumor response. Patients entering the trial had previously been treated with a median of three, and as many as eleven prior lines of systemic therapy. TK216 has been generally well tolerated in this trial, with common side effects including myelosuppression, fatigue, nausea and alopecia. Dose limiting toxicities consisted of transient and manageable myelosuppression, primarily neutropenia. No unexpected off-target toxicities have been observed. The recommended Phase 2 dose (RP2D) has been established to be 200 mg/m2/day of TK216 for 14 days in combination with vincristine chemotherapy dosed at 0.75 mg/m2 on the first day of each treatment cycle.

Key Updates: The presentation included interim data for 15 evaluable patients treated at the RP2D as of the August 13, 2020 cut-off date. Two of the 15 patients have now achieved complete responses (CR), including one surgical CR. One of these patients was previously categorized as a partial responder after two treatment cycles and converted to a complete response after his 6th cycle. Five patients had stable disease (SD), for a disease control rate (CR, partial response or SD) of 47%.

The first patient achieving a CR initially presented with metastatic Ewing sarcoma involving the clavicle and lungs and had received four prior lines of systemic therapy as well as surgery and radiation and was progressing when he enrolled in this clinical trial. The patient experienced a deep and sustained partial clinical response following two cycles of TK216 alone, with resolution of all target lung metastases. After six months of treatment that included concomitant vincristine starting in the third cycle, a single 7 mm lung nodule was resected, resulting in a surgical complete remission. The patient remains on treatment, with no evidence of disease, at about 1.5 years in this clinical trial.

The second patient achieving a CR initially presented with metastatic Ewing sarcoma involving the kidney area and lungs. He relapsed following initial chemotherapy, radiation, and surgery before enrolling in this clinical trial. The patient achieved a partial response with a 90% reduction of all lesions following two cycles of therapy and achieved a complete response after six cycles. The patient remains on treatment, with no evidence of disease at about seven months in this clinical trial.

Pharmacokinetic data from the clinical trial showed that TK216 drug levels at the RP2D exceeded plasma levels associated with anti-tumor activity in preclinical models.

"We are excited by the deepening clinical responses over time, with now two complete responses reported for patients with Ewing sarcoma treated with TK216," said James Breitmeyer, M.D., Ph.D., President and CEO, Oncternal. "Enrollment in the expansion cohort of this clinical trial has accelerated despite the COVID-19 pandemic, and we plan to present additional data from over 16 patients with relapsed/refractory Ewing sarcoma treated at the RP2D at a scientific conference in the fourth quarter of 2020."

About TK216

TK216 is an investigational, potentially first-in-class, targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as prostate cancer and acute myeloid leukemia (AML). TK216 was developed based on discoveries in the laboratory of Jeffrey Toretsky, M.D., at Georgetown Lombardi Comprehensive Cancer Center, who discovered inhibitors of EWS-FLI1 using a novel chemical screening assay. In preclinical models, TK216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Orphan Designation and Fast Track designation to TK216 for the treatment of Ewing sarcoma. TK216 is an investigational medication that has not been approved by the FDA for any indication.

About the Study

TK216 is being evaluated in a Phase 1 clinical study as a single agent and in combination with vincristine in patients with relapsed or refractory Ewing sarcoma, a rare pediatric cancer with no standard treatment available after first-line chemotherapy. The dose-finding portion of the study is complete, and patients are now being enrolled in the expansion cohort. This multi-center study is actively enrolling patients at nine clinical trial centers across the U.S. Additional information about the TK216 study may be accessed at ClinicalTrials.gov (NCT02657005).

On September 21, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX) a biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the initiation of a Phase 1 clinical trial in China for ON 123300 by its partner, HanX Biopharmaceuticals (Press release, HanX Biopharmaceuticals, SEP 21, 2020, View Source [SID1234565437]).

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In December 2017, Onconova entered into an agreement with HanX Biopharmaceuticals for the development, registration, and commercialization of ON 123300 in China. The agreement included a licensing fee, and future potential milestone payments and royalties on sales. Outside of China, Onconova retains rights in rest of the world.

ON 123300 is a novel small molecule, and a dual inhibitor of CDK4/6 and ARK5, a key enzyme controlling cellular energy homeostasis. Inhibition of ARK5 by ON 123300 results in the collapse of oncogene-altered energy metabolism, leading to programmed cell death. Differentiated from health authority approved CDK4/6 inhibitors, ON 123300 exhibits single agent toxicity against various cancers in preclinical studies including breast cancer, colon cancer, mantle cell lymphoma and multiple myeloma.

"As a proprietary first-in-class anti-cancer agent, ON 123300 is reported to have a unique dual mechanism of action that could improve upon the clinical efficacy of approved CDK4/6 inhibitors and may impact on the development of metastatic disease, while potentially mitigating the commonly observed side effects based on animal studies already conducted," said Steven M. Fruchtman, M.D., President and Chief Executive Officer. "We look forward to filing our US IND by the end of this year and beginning a US Phase 1 study in refractory solid tumors in the first quarter of next year."

On September 21, 2020 Cyclacel Pharmaceuticals, Inc. (Nasdaq: CYCC) (Nasdaq: CYCCP) (Cyclacel or the Company), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported that an abstract highlighting clinical data with Cyclacel’s CDK2/9 inhibitor fadraciclib has been selected for an oral presentation at the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium 2020 being held virtually on October 24 – 25, 2020 (Press release, Cyclacel, SEP 21, 2020, View Source [SID1234565436]). The data is from an ongoing Phase 1 study of fadraciclib as a single agent in patients with advanced solid tumors.

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Details for the presentations are as follows:

Title: Phase 1 safety, pharmacokinetic and pharmacodynamic study of fadraciclib (CYC065), a cyclin dependent kinase inhibitor, in patients with advanced cancers (NCT02552953)
Session Title: Late Breaking and Best Proffered Papers
Session Date and Time: Saturday 24 October 15:05 CET
Presentation Number: ORAL-002

The program can be accessed through the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) website.

About Cyclin-Dependent Kinases and Fadraciclib

Cyclin-dependent kinases (CDKs) are critical for cell cycle regulation and transcriptional elongation. Dysregulated CDKs have been linked to the cancer hallmarks of uncontrolled proliferation and increased survival. Fadraciclib (CYC065) is a potent orally and intravenously available inhibitor of CDK2 and CDK9.

In part 1 of a Phase 1, first-in-human study of fadraciclib as a single agent in patients with advanced solid tumors, target engagement and durable suppression of the MCL1 biomarker were observed after a single dose of fadraciclib. Tumor shrinkage and stable disease were observed in five patients with cyclin E, MCL1 and/or MYC amplified cancers.

The ongoing part 2 of the study is evaluating a more intensive dosing regimen than part 1. A heavily pretreated patient with MCL1 amplified endometrial cancer achieved a radiographically confirmed partial response (PR) after a month and a half on fadraciclib. Fadraciclib is also being evaluated in Phase 1 combination studies with venetoclax in patients with relapsed or refractory CLL and AML/MDS.

Preclinical data suggest that fadraciclib may benefit patients with adult and pediatric hematological malignancies such as AML, ALL, B-cell lymphomas, CLL, multiple myeloma and certain cyclin E-addicted or MYC-amplified solid tumors, including certain forms of breast cancer, neuroblastoma, ovarian cancer and uterine serous carcinoma.

On September 21, 2020 TLC (Nasdaq: TLC, TWO: 4152), a clinical-stage specialty pharmaceutical company developing novel nanomedicines to target areas of unmet medical need, reported that President Mr. George Yeh and Chief Medical Officer Dr. George Spencer-Green, MD, will be presenting at Oppenheimer Fall Healthcare Life Sciences & Med Tech Summit on Wednesday, September 23, 2020 at 9:10am ET (Press release, Taiwan Liposome Company, SEP 21, 2020, View Source [SID1234565435]).

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The 40-minute live presentation will include a company overview and update by Mr. Yeh, with analyses of data on TLC’s pain programs – TLC599 and TLC590 – by Dr. Spencer-Green. During the virtual conference, which takes place September 21-23, 2020, TLC will also be participating in one-on-one sessions.

The corporate presentation is available on the TLC website at www.tlcbio.com in the Investors section, under News & Events.