On December 9, 2019 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the presentation of updated interim clinical data from the ongoing Phase 1/2 CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and Lymphoma) clinical trial, in which cirmtuzumab, an investigational anti-ROR1 monoclonal antibody, is being evaluated in combination with ibrutinib in patients with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) (Press release, Oncternal Therapeutics, DEC 9, 2019, View Source [SID1234552138]). The results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando. A copy of the poster presentation is available online at www.oncternal.com.

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Thirty-four patients with CLL who had never been treated with a BTK inhibitor were enrolled in the dose-finding and dose-confirming cohorts of this clinical trial, including 12 treatment-naïve and 22 relapsed/refractory patients, and all 34 were evaluable for efficacy. As of the data cut-off in early November 2019,

Twenty-nine of the 34 patients achieved a response, for an overall best objective response rate of 85%.
One patient achieved a complete response (CR) and remained in remission six months after completion of the trial and discontinuation of all anti-CLL therapy. In addition, three patients met radiographic and hematologic response criteria for Clinical CR, bone marrow biopsy not performed but pending.
Five patients had stable disease.
The total clinical benefit rate was 100%.
None of the patients progressed or died, for a progression-free survival (PFS) of 100% with a median follow-up of 7.4 months.
Patients achieved responses rapidly, with 68% of patients achieving a clinical response by three months on combination therapy.
The rise in leukemic cell counts that is typically seen in the first six months with ibrutinib monotherapy was blunted with the cirmtuzumab plus ibrutinib combination, and leukemic cell counts returned toward baseline and normal levels rapidly.
Twelve patients with relapsed/refractory MCL, eight of whom were evaluable for efficacy, were enrolled in the dose-finding cohort of this trial. As of the data cut-off, five of the eight evaluable patients had achieved a clinical response, for an overall best objective response rate of 63% at a median follow-up of six months. Two patients with aggressive or bulky and heavily pre-treated MCL achieved CR, the longest of which is continuing with the patient on study for over 17 months. In addition, three patients had stable disease, for a total clinical benefit rate of 100%.

Cirmtuzumab as a single agent has been very well tolerated in this study. The combination of cirmtuzumab plus ibrutinib has also been well tolerated, with adverse events consistent with those reported for ibrutinib alone. There have been no dose limiting toxicities and no serious adverse events attributed to cirmtuzumab alone.

Genetic analysis of CLL cells from three patients showed pre-treatment transcriptome profiles associated with a stemness signature and NF-kB-driven inflammation. Both genetic signatures were reversed in these patients following cirmtuzumab treatment.

"It is exciting to see that cirmtuzumab in combination with ibrutinib continues to be well tolerated and has demonstrated 100% progression-free survival in patients with CLL, as well as encouraging early signals of efficacy in patients with MCL," said Michael Choi, M.D., Associate Clinical Professor of Medicine in the Division of Hematology-Oncology at University of California San Diego School of Medicine, who is the lead investigator for the CIRLL clinical trial.

The CIRLL clinical trial is supported by a grant from the California Institute for Regenerative Medicine (CIRM) and is being conducted in collaboration with the UC San Diego School of Medicine.

"We are encouraged by the evidence of clinical activity and the safety data demonstrated by cirmtuzumab in the ongoing CIRLL clinical trial. We continue to be excited about its potential for the treatment of patients with ROR1-expressing cancers, including CLL, MCL, Her2-negative breast cancer and other solid tumors," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO.

About the CIRLL Clinical Trial

The CIRLL clinical trial (CIRM-0001) is a Phase 1/2 trial evaluating cirmtuzumab in combination with ibrutinib in separate groups of patients with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). Part 1 of the clinical trial was a Phase 1 dose-finding cohort designed to determine the Phase 2 dose, or recommended dosing regimen (RDR). Part 2 is a Phase 1b expansion cohort to confirm the RDR. Part 3 of the study, which is now open for enrollment, is a Phase 2 study in which approximately 90 patients with CLL will be randomized to receive either ibrutinib alone or ibrutinib plus cirmtuzumab, with a primary endpoint of complete response rate. Additional information about the CIRM-0001 clinical trial and other clinical trials of cirmtuzumab may be accessed at ClinicalTrials.gov.

About Cirmtuzumab

Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of CLL and MCL, in a collaboration with the University of California San Diego School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with metastatic breast cancer is being conducted at the UC San Diego School of Medicine. CIRM has also provided funding to support development programs for cirmtuzumab and a CAR-T therapy that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors.

ROR1 is a potentially attractive target for cancer therapy because it is an oncofetal antigen – a protein that confers a survival and fitness advantage when reactivated and expressed by tumor cells. When expressed by hematologic malignancies such as CLL and MCL, ROR1 acts as a receptor for the tumor growth factor Wnt5a. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to inhibiting Wnt5a activation, specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when cirmtuzumab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. Cirmtuzumab is in clinical development and has not been approved by the U.S. Food and Drug Administration for any indication.

On December 9, 2019 SCYNEXIS, Inc. (NASDAQ : SCYX) reported that it has commenced an underwritten public offering of shares of its common stock and warrants (Press release, Scynexis, DEC 9, 2019, View Source [SID1234552154]). In addition, SCYNEXIS expects to grant the underwriter a 30-day option to purchase up to an additional 15% of the shares of common stock and warrants being offered on the same terms and conditions. All of the shares of common stock and warrants in the offering will be sold by SCYNEXIS. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed or as to the actual size or terms of the offering.

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H.C. Wainwright & Co. is acting as sole book-running manager for the offering.

A shelf registration statement relating to the shares being sold in this offering was filed with the U.S. Securities and Exchange Commission on August 31, 2018, and was declared effective on September 14, 2018. The offering will be made only by means of a prospectus supplement and accompanying prospectus. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available for free on the SEC’s website located at View Source When available, electronic copies of the preliminary prospectus supplement and accompanying prospectus relating to the proposed public offering may be obtained by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, or by telephone at (646) 975-6996, or by email to [email protected]. This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 9, 2019 Australian life sciences company, QBiotics Group Limited (QBiotics) is reported the publication[1] of positive results from a first in-human Phase I clinical trial of its anticancer pharmaceutical, tigilanol tiglate (EBC-46) in EBioMedicine, a peer-reviewed translational biomedical research journal by The Lancet (Press release, QBiotics, DEC 9, 2019, View Source;efficacy-of-tigilanol-tiglate-in-solid-tumours-300971159.html [SID1234552170]).

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The key objectives of this Phase I, open-label, single-arm, non-randomised, dose-escalation study were to determine the safety profile, tolerability, pharmacokinetics (PK), and preliminary antitumour efficacy of tigilanol tiglate when administered once by intratumoural injection. Tigilanol tiglate was generally well tolerated and doses escalated from 0.06 to 3.60 mg/m[2], without reaching a maximum tolerated dose.

The study was conducted in 22 patients at four hospital sites in Australia[1]. Patients were recruited with a range of tumour types including squamous cell carcinoma, basal cell carcinoma, melanoma, breast adenocarcinoma, atypical fibroxanthoma, atypical myxoid fibrosarcoma, metastatic colorectal adenocarcinoma, adenoid cystic carcinoma and angiosarcoma. Signs of clinical activity were observed in all nine tumour types, even at the lowest doses.

"As this was a first-in-human, single dose safety study, the expectation of a strong anticancer response was low. However, the results revealed a 27% treatment response (in 6 patients), including an 18% complete response (in 4 patients) with full tumour destruction across a wide variety of solid tumour types.

"Solid tumours account for up to 80% of all tumour types,[3] so the results from this Phase I study indicate potentially broad applications for tigilanol tiglate in a range of tumours, and an important advancement for our pharmaceutical," said QBiotics Group CEO and Managing Director, Dr Victoria Gordon.

"Additionally, two patients with melanoma demonstrated an anenestic (or abscopal) response, where non-injected tumours at different locations in the body also reduced in size. These results were achieved despite many patients not receiving an optimal dose,[1]" added Dr Gordon.

The vast majority (96%) of adverse events (AEs) were mild to moderate, with the most commonly reported AE being injection site reaction related to the mode of action of tigilanol tiglate. AEs were generally managed with symptomatic therapy.[1]

"Given the very good safety profile, and positive antitumour responses observed, this study supports further development of tigilanol tiglate as a potential treatment of solid tumours," said Dr Gordon

"Results from this study also underpins selection of our initial lead indication and our recently announced Phase I/II trial of tigilanol tiglate in patients with Head and Neck Squamous Cell Carcinoma (HNSCC), in which the first patient was successfully dosed last week," Dr Gordon said.

The Phase I/II open label "QBC46-H03" study, is a dose escalation study in patients with HNSCC aimed at determining the maximum tolerated dose (MTD) and recommended dose level for further studies. The study will also investigate safety, tolerability and tumour response following single or multiple (two to three) doses of tigilanol tiglate. It will enrol up to 40 patients from the Tata Medical Centre in Kolkata, the Tata Memorial Hospital in Mumbai, and other clinical sites in Australia.

ISSUED BY

QBIOTICS GROUP LIMITED – www.QBiotics.com

FOR FURTHER
INFORMATION

DR VICTORIA GORDON, CEO & MANAGING DIRECTOR, QBIOTICS GROUP
[email protected] or + 61 418 453 737

On December 9, 2019 Qilu Pharmaceutical reported that The National Medical Products Administration approved it’s Ankeda as a biosimilar to Avastin (bevacizumab) for the treatment of multiple types of cancer (Press release, Qilu Pharmaceutical, DEC 9, 2019, View Source [SID1234595070]). Ankeda is the first Avastin biosimilar approved in China for the treatment of cancer.

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The NMPA’s approval of Ankeda is based on review of evidence that includes extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Ankeda is biosimilar to Avastin.

Qilu made big investment on Ankeda development. It took less than 1.5 years for the NMPA to greenlight Qilu’s Ankeda. Qilu is committed to bringing more biosimilars to patients to help lower healthcare costs and increase access to important therapies.

On December 9, 2019 ArQule, Inc. (Nasdaq: ARQL) reported final results from the phase 1 study for ARQ 531, an orally bioavailable, potent and reversible dual inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK) in patients with relapsed or refractory hematologic malignancies at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 Annual Meeting & Exposition in Orlando, Florida (Press release, ArQule, DEC 9, 2019, View Source [SID1234552104]).

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"The final phase 1 data set confirms the potential utility of ARQ 531 for the treatment of these heavily pretreated CLL patients. We were excited to observe such deep and durable responses at a well-tolerated dose in this highly refractory population," commented Dr. Brian Schwartz, Chief Medical Officer of ArQule. "In addition, the three responses we observed in Richter’s Transformation patients were a welcome outcome and allowed several patients to transition to potentially curative therapies."

"ARQ 531 was selected and extensively tested preclinically to address the emerging therapeutic needs of patients who have become resistant to covalent BTK inhibitors in a broad set of hematologic malignancies," commented Dr. Jennifer Woyach, Associate Professor of Medicine at The Ohio State University and the Principal Investigator of the study. "It is tremendously gratifying to witness the emergence of a potential therapeutic for patients with such a high degree of unmet need, such as C481S-mutant CLL and Richter’s Transformation, and beyond. The data presented in this poster provide compelling proof-of-concept for this novel class of reversible BTK inhibitors."

The reported data are from the phase 1, open label, single arm dose escalation study and include patients (n=47) initially dosed at levels of 5, 10, 15, 20, 30, 45, 65 and 75 mg once a day with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), Richter’s Transformation, Waldenström macroglobulinemia and other B-cell Non-Hodgkin lymphomas.

Key Findings:

65 mg QD was selected as the Recommended Phase 2 Dose (RP2D) for further studies
Across all disease subsets, ARQ 531 showed a low incidence of associated toxicities, including one grade three DLT and no atrial fibrillation or bleeding observed
At 65 mg QD, ARQ 531 has a steady state mean Cmin above 1 µM and long plasma half-life of 56 hours resulting in complete pBTK inhibition
Clinical Anti-Tumor Activity:
In CLL, an Overall Response Rate (ORR) of 89% (8/9 responses in evaluable patients) was achieved in heavily pretreated R/R CLL patients (7/8 harboring BTK-C481S mutation) dosed at ≥65 mg QD. Eleven of 19 patients treated at 65 mg QD remain on study
In Richter’s Transformation, an ORR of 50% (3/6 responses in evaluable patients) was achieved at 65 mg QD
Two additional PRs were observed including one patient with Follicular Lymphoma (FL) and 1 patient with Diffuse Large B-cell Lymphoma (DLBCL)
Durability:
100% (5/5) evaluable CLL patients that received a third scan (cycle 9) are durable confirmed PRs and remain on therapy
67% (2/3) of Richter’s patients that achieved PRs came off study after becoming eligible for CAR-T therapy
The Follicular Lymphoma patient that achieved a PR has been on study for 120 weeks and remains a PR and on therapy
The poster at ASH (Free ASH Whitepaper) presenting these data entitled, "Final Results of Phase 1, Dose Escalation Study Evaluating ARQ 531 in Patients with Relapsed or Refractory B-Cell Lymphoid Malignancies," is available on the company’s website at www.arqule.com/publications-presentations/.

In addition, earlier today Merck and ArQule announced that the companies have entered into a definitive agreement under which Merck, through a subsidiary, will acquire ArQule. A copy of the joint press release is available on ArQule’s website, www.arqule.com.

ArQule will host a conference call and webcast for investors on Monday, December 9, 2019 at 8:15 a.m. EST to discuss the ARQ 531 clinical data. The live webcast can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events & Presentations" or by visiting click here. You may also listen to the call by dialing (877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. and providing conference ID 4573858. A replay will be available two hours after the completion of the call and can be accessed in the "Investors & Media" section of our website, www.arqule.com, under "Events and Presentations."

ArQule management will host an Investor Event to answer questions and discuss these data in Orlando tonight, Monday, December 9, 2019 from 8:00–10:00 p.m. EST. Investors, sell side analysts, and industry representatives are welcome to attend. For event details and to RSVP, please email [email protected].

About BTK and ARQ 531

Bruton’s tyrosine kinase, BTK, is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers. ARQ 531 is an orally bioavailable, potent and reversible dual inhibitor of both wild type and C481S-mutant BTK. The C481S-mutation is a known resistance mechanism for first generation irreversible BTK inhibitors. ARQ 531 has demonstrated a manageable safety profile, predictable PK, convincing pharmacodynamic effects and signs of clinical activity.