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ArQule Announces Clinical Proof-of-Concept Data from Ongoing Phase 1 Study of Reversible BTK Inhibitor, ARQ 531, in Patients with Relapsed/Refractory Hematologic Malignancies at the 2019 EHA Annual Meeting

On June 14, 2019 ArQule, Inc. (Nasdaq: ARQL) reported preliminary results from the Company’s phase 1 dose escalation 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 2019 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in Amsterdam, the Netherlands (Press release, ArQule, JUN 14, 2019, View Source [SID1234537072]).

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"The profile of ARQ 531 continues to strengthen, and we are delighted to be able to demonstrate such compelling clinical activity at a well-tolerated dose in patients who have already exhausted available therapies," commented Dr. Brian Schwartz, Chief Medical Officer of ArQule. "We are now focused on finalizing the recommended phase 2 dose and planning for the expansion of our clinical efforts with ARQ 531 into later stage trials across multiple indications as a single agent and as a combination therapy."

"ARQ 531 was selected and extensively tested preclinically to address the emerging therapeutic need for patients who have become resistant to covalent BTK inhibitors," commented Dr. Jennifer Woyach, Associate Professor of Medicine at The Ohio State University and the Principal Investigator of the study. "The data presented in this poster provide compelling clinical proof-of-concept for this novel class of reversible BTK inhibitors and was predicted by the preclinical studies published in Cancer Discovery1 last year."

The reported data are from the ongoing phase 1, open label, single arm dose escalation study and include the first eight cohorts (n=34) at dose levels of 5, 10, 15, 20, 30, 45, 65 and 75 mg once a day in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), Richter’s Transformation, Waldenström macroglobulinemia and other B-cell Non-Hodgkin lymphomas. Cohort 8 (75 mg) enrollment is ongoing.

Key findings presented include the following:

ARQ 531 is well-tolerated through 65 mg QD
Pharmacokinetic data demonstrate a steady-state mean Cmin of above 1 µM in patients receiving ≥45 mg QD. The plasma half-life ranges from 20-30 hours
Pharmacodynamic data at doses above 20-30 mg QD is associated with complete pBTK inhibition and substantial CCL3 suppression
Robust, dose-dependent, anti-tumor activity was observed
ORR of 66% (4 responses in 6 evaluable patients) was observed in heavily pretreated R/R CLL patients, all with the BTK-C481S mutation, from cohort 7
A partial response was observed in the first patient with Richter’s Transformation, who had progressed on ibrutinib and R-CHOP, suggesting that ARQ 531’s distinct MOA is amenable to target this highly unmet medical need
A Follicular Lymphoma patient remains a confirmed PR and has been on therapy approximately two years, providing valuable initial insights into long- term safety as well as durability of response
The poster at EHA (Free EHA Whitepaper) presenting these data entitled, "A Phase 1 Dose Escalation Study of 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/.

ArQule will host a conference call and webcast for investors on Friday, June 14, 2019 at 8:00 a.m. EDT 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 clicking here. You may also listen to the call by dialing 1-800-239-9838 within the U.S. or 1-323-794-2551 outside the U.S. and providing conference ID 3110780. 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."

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 good safety profile, predictable PK, profound pharmacodynamic effects and emerging signs of dose-proportional clinical activity in phase 1 clinical testing.

NIH Awards Bound Therapeutics LLC $300,000 in Grant Funding

On June 13, 2023 Bound Therapeutics reported the US National Cancer Institute has awarded Bound Therapeutics LLC a Small Business Technology Transfer grant starting 15 June for $300,000 to develop "microRNA-21 Blockade of Triple Negative Breast Cancer" (Press release, Bound Therapeutics, JUN 13, 2019, View Source [SID1234637827]).

"Triple negative breast cancer strikes younger women, tragically killing half the patients within 4 years," said Dr. Yuan-Yuan Jin, Chief Operating Officer of Bound Therapeutics LLC. "Surgery, chemotherapy, and radiation are the current standard of care for triple negative breast cancer."

"To provide effective molecular therapy that will keep patients alive with a good quality of life, we have designed a cancer cell-targeted drug that will block a tiny strand of ribonucleic acid, called microRNA-21," explained Dr. Eric Wickstrom, Professor of Biochemistry and Molecular Biology at Thomas Jefferson University, a partner in the award.

Dr. Miguel Castro, President and CEO of Bio-Synthesis Inc., another research partner, said that "The RNA analogs and peptide analogs that we are making to treat triple negative breast cancer cells are extraordinarily specific and safe in mammalian models."

Our clinical collaborator, Dr. Edith Mitchell, Clinical Professor of Medicine and Medical Oncology at Thomas Jefferson University, commented that "Patients with triple negative disease have limited treatment options compared to patients with more common forms of breast cancer. There is an urgent need for targeted treatments in this area." Dr. Mitchell serves as the Director of the Jefferson Center to Eliminate Cancer Disparities in diagnosis, treatment, and survival of patients with different ancestries, and is a past President of the National Medical Association.

GT BIOPHARMA GTB-1550

On June 13, 2019 GT Biopharma, Inc. (OTCQB: GTBP) (GTBP.PA) an immuno-oncology company reported that developing GTB-1550, a novel multi-target bispecific drug conjugate therapy for the treatment of chemotherapy-refractory B-cell malignancies (Press release, GT Biopharma , JUN 13, 2019, View Source [SID1234539511]).

Today, Bloomberg discussed antibody-drug conjugates (ADC) as effective cancer therapies having the potential to replace traditional chemotherapy. ADCs are essentially a "trojan horse" therapeutics which have several advantages over traditional chemotherapy including less toxicity and higher efficacy due to a more precise targeting of cancer cells compared to non-cancer cells.

An ADC is composed of an antibody which specifically identifies cancer cells and a cytotoxic agent (the payload) which has been grafted onto the antibody. When injected into patients, the ADC traffics through the patient’s body to find the targeted cancer cells. Upon binding to the cancer cell, the ADC is internalized by the cancer cell, and the cytotoxic payload kills the cancer cell.

Anthony Cataldo (CEO GT Biopharma, Inc.) said, "The Bloomberg article points out the excitement that big pharma is now realizing as the potential for ADC’s as a realistic alternative to Chemo Therapies. What differentiates our ADC Bispecific GTB-1550, is the ability for our drug to hit multiple target sites of B-cell malignancies as opposed to the one target ADC’s represented in the Bloomberg article. We are happy to see the attention of the large pharmaceuticals moving in this direction."

GTB-1550 is a novel, multi-target bispecific cytotoxic therapeutic agent consisting of diphtheria toxin and bispecific single-chain variable fragments (scFV) of antibodies targeting human CD19 and CD22. By simultaneously targeting cancer cells that express either CD19 or CD22 or both, GTB-1550 is capable of killing a broader variety of hematological malignancies than either a traditional a CD19 antibody drug conjugate or a CD19 CAR-T immunotherapy which are only able to target and attack CD19 expressing hematological malignancies. Simultaneously targeting multiple cancer targets such as CD19 and CD22 using a single therapeutic agent potentially makes GT Biopharma’s multi-target bispecific drug conjugate therapy the next generation of advanced cancer therapies.

To date, GTB-1550 has completed one dose escalation Phase I-II expansion clinical trial, and one fixed dose Phase I-II expansion clinical trial which collectively enrolled a combined 43 patients.

Top-line Consolidated Results:

Two patients exhibited a Complete Remission (CR) with one patient currently disease-free at 50 months post treatment.
Five patients exhibited Stable Disease (SD) with the longest response lasting 12 months post treatment.
Two patients with transformed lymphoma showed transient tumor shrinkage, however, therapy was discontinued due to dose-limiting toxicities after the 1st cycle.
Greater than 50% of evaluable patients receiving 60 mg/kg dose had positive clinical response defined as stable disease, partial remission, or complete remission.

I-Mab Announces IND Approval for Its Proprietary TJC4, A Potentially Differentiated CD47 Antibody, to Initiate Clinical Trials in China

On June 13, 2019 I-Mab Biopharma ("I-Mab"), a clinical stage biotech company exclusively focusing on discovery and development of innovative biologics in immuno-oncology and autoimmune diseases, reported that the National Medical Products Administration (NMPA) has approved its investigational new drug (IND) application for TJC4, a differentiated fully human CD47 monoclonal antibody internally developed for the treatment of advanced malignant tumors (Press release, I-Mab Biopharma, JUN 13, 2019, View Source [SID1234537516]). Previously on June 24, 2019, I-Mab announced the first patient dosing of TJC4 in a phase I clinical study in the US.

As a pivotal drug candidate from I-Mab’s innovative pipeline, TJC4 is a potential global best-in-class CD47 Monoclonal Antibody. Unlike other known CD47 antibodies under development, it binds to a unique epitope on CD47 that leads to minimal red blood cell binding, resulting in neither hemagglutination in vitro nor anemia in cynomolgus monkeys in toxicological studies.

"We are delighted to receive the IND clearance of TJC4 from the NMPA to start clinical studies in China. This is another significant progress after we initiated the phase 1 study in the United States," Expressed by Dr. Joan Shen, Head of R&D at I-Mab, "By design and from the pre-clinical data, we believe TJC4 has the great potential to become a best-in-class agent treating cancer patients worldwide."

About CD47 and TJC4
CD47 is a glycoprotein over-expressed in a wide variety of cancers and delivers a "don’t eat me" signal to tumor-engulfing macrophage through its ligand known as SIRPα. Blockade of CD47 by TJC4 enables macrophage to engulf cancer cells as a potential treatment option for cancers. TJC4 also known as TJ011133 is a differentiated CD47 monoclonal antibody and designed to minimize inherent binding to normal red blood cells by this class of monoclonal antibodies yet preserve its strong anti-tumor activities. TJC4 recognizes a unique epitope on CD47 and exhibits a minimal binding to red blood cells. The hematologic safety advantage of TJC4 has been demonstrated in a series of robust pre-clinical and toxicological studies including those in cynomolgus monkeys, while it maintains superb anti-tumor activities.

Savara to Present at the JMP Securities Life Sciences Conference

On June 13, 2019 Savara Inc. (Nasdaq: SVRA), an orphan lung disease company, reported that the Company’s Chief Executive Officer, Rob Neville, and Chief Operating Officer, Taneli Jouhikainen, will present at the JMP Securities Life Sciences Conference on Wednesday, June 19, 2019 at 11:30 a.m. Eastern Time / 8:30 a.m. Pacific Time in the Fontainebleau room, The St. Regis, New York (Press release, Savara, JUN 13, 2019, View Source [SID1234537090]).

Interested parties can access a live audio webcast on the Investors page of the Savara website at www.savarapharma.com/investors/events-presentations/. Please connect to the Company’s website at least 15 minutes prior to the start of the presentation to ensure sufficient time for any software download that may be required for the webcast. An archived presentation will be available on Savara’s website for 30 days.