On September 10, 2018 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, reported the publication of results from a Phase 1b clinical trial combining TRC105 with Inlyta (axitinib) in patients with advanced or metastatic renal cell carcinoma (RCC) (Press release, Tracon Pharmaceuticals, SEPT 10, 2018, View Source [SID1234529373]). Dr. Toni Choueiri of the Dana Farber Cancer Institute and colleagues published these results in the peer-reviewed journal, The Oncologist (Epublication ahead of print is available at PubMed.gov through PubMed ID number 30190302), and Dr. Andrew Hahn of the Huntsman Cancer Institute and co-authors published an accompanying editorial (Epublication ahead of print is available at PubMed.gov through PubMed ID number 30139834). These data were previously presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, Denmark.

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The open-label dose escalation and expansion Phase 1b study enrolled a total of 18 patients (17 of whom were evaluable for response) who had received at least one prior line of therapy with a VEGF receptor tyrosine kinase inhibitor (VEGFR TKI). The median number of prior therapies in the group was three, with a range of one to six. All patients in the trial received a combination of TRC105 and Inlyta. The data are summarized in the table below.

For comparison, in a separate trial, the objective response rate (ORR) seen in the large subgroup of VEGFR TKI-refractory patients treated with Inlyta (n=194) in the Inlyta AXIS Phase 3 study in second-line clear cell RCC patients was 11.3%, and median progression-free survival (PFS) was 4.8 months.

The publication also notes that plasma levels of TGF-β receptor 3 (betaglycan) at baseline were significantly higher in patients who experienced a partial response, while levels of osteopontin were significantly lower at baseline for patients that achieved a partial response. Both markers correlated with time on study and their potential prognostic value are being investigated in the ongoing Phase 2b TRAXAR study. TRACON’s Phase 2b TRAXAR clinical trial of TRC105 in combination with Inlyta completed enrollment of 150 patients with advanced or metastatic RCC in Q3 2017 and top-line data are expected to be available in December 2018.

About the TRAXAR Phase 2b Clinical Trial in RCC

The Phase 2b TRAXAR clinical trial is a multicenter, open-label, randomized clinical trial of TRC105 in combination with Inlyta versus Inlyta in patients with advanced or metastatic RCC. The primary endpoint of the Phase 2b study is progression-free survival. Patients may have also failed one prior mTOR inhibitor and one prior immunotherapy. For additional information on this clinical trial, please visit www.clinicaltrials.gov, identifier NCT01806064.

About Carotuximab (TRC105)

TRC105 is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in a pivotal Phase 3 trial in angiosarcoma and multiple Phase 2 clinical trials, in combination with VEGF inhibitors, as well as in a Phase 1 trial with Opdivo. TRC105 has received orphan designation for the treatment of soft tissue sarcoma in both the U.S. and EU. The ophthalmic formulation of TRC105, DE-122, is currently in a randomized Phase 2 trial for patients with wet AMD. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

On September 10, 2018 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported business highlights and financial results for the fiscal year 2018 third quarter, ended July 31, 2018 (Press release, Advaxis, SEPT 10, 2018, View Source [SID1234529374]).

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Recent key accomplishments include:

Dosing of the first patient in the Company’s Phase 1 trial with ADXS-NEO, a personalized immunotherapy approach targeting neoantigens identified by sequencing a patient’s own cancer cells, partnered with Amgen.
U.S. Food and Drug Administration (FDA) allowance of the Company’s Investigational New Drug (IND) application for its first ADXS-HOT drug candidate, ADXS-503, for non-small cell lung cancer. ADXS-HOT is an off-the-shelf cancer-type specific immunotherapy approach that leverages the Company’s proprietary Lm technology platform to target hotspot mutations and other tumor-associated antigens that commonly occur in specific cancer types.
Selecting prostate and bladder cancers as the second and third ADXS-HOT drug candidates to take into the clinic.
Granting of a license to OS Therapies for the use of ADXS31-164, also known as ADXS-HER2, for evaluation in the treatment of osteosarcoma, a rare and aggressive tumor that forms in the bone.
Pricing of its public offering of common stock and warrants. The planned underwritten public offering is expected to result in gross proceeds of approximately $20 million and close on or around September 11, 2018.
Management Commentary

"We are encouraged by the momentum achieved with both of our neoantigen-focused programs during our third fiscal quarter and continue on our path of achieving our goal of having five neoantigen-based product candidates in clinical evaluation by the end of 2019," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "We believe in the powerful impact neoantigens may have on the cancer treatment paradigm. Several of the unique attributes of our Lm platform including the capacity of our vector to contain a large number of neoantigens in each single drug construct, as well as the vector’s ability to generate strong T-cell responses to neoantigens as demonstrated in previously reported studies, provide us with an opportunity to lead in this potentially revolutionary field of cancer treatment.

"ADXS-NEO, partnered with Amgen, takes a personalized approach to therapy and has the potential to make an important contribution among underserved cancer patient populations with few or no treatment options," he added. "Similarly, the IND allowance by the FDA of our ADXS-HOT drug candidate for non-small cell lung cancer enables us to finalize our Phase 1 trial design and dose our first patient by the end of the year. The ADXS-HOT program, in general, is focused on shared hotspot mutations and other cancer antigens commonly found in cancers with large patient populations such as non-small cell lung cancer and prostate cancer."

"We are also excited about the licensing transaction executed with OS Therapies to evaluate our HER-2 therapy for the treatment of human osteosarcoma. This is a product candidate we believe in, although it falls outside our neoantigen focus. The transaction supports continued clinical development by a team of experts exclusively focused on finding new treatments for osteosarcoma and allows us to remain dedicated to our corporate strategy," he added.

Financial Results for Third Quarter Fiscal Year 2018

The net loss for the third quarter ended July 31, 2018 was $14.0 million or $0.27 per share. This compares with a net loss for the third quarter of fiscal year 2017 of $32.6 million or $0.80 per share. The $18.6 million reduction in the net loss compared to prior year was primarily a result of the significant reduction in spending in research, development and administrative areas.

Research and development expenses for the third quarter of fiscal year 2018 were $10.8 million, compared with $17.8 million for the third quarter of fiscal year 2017. The decrease is primarily attributable to a decrease in laboratory costs, drug manufacturing process validation and drug stability studies supporting the MAA, which we withdrew in July 2018.

General and administrative expenses for the third quarter of fiscal year 2018 were $4.5 million, compared with $18.0 million for the third quarter of fiscal year 2017. The decrease is primarily attributable to a decrease in stock-based compensation of approximately $11.4 million related to the resignation of the Company’s Chief Financial Officer and Chief Executive Officer in April 2018 and July 2017, respectively, two Board members who did not seek re-election in March 2018, a reduction in headcount and the elimination of stock-based compensation paid to consultants.

Balance Sheet Highlights

As of July 31, 2018, the Company had approximately $40.4 million in cash, restricted cash and cash equivalents on its balance sheet. The Company is anticipating closing on an underwritten public offering of its common stock and warrants on or around September 11, 2018 which is expected to result in gross proceeds of approximately $20 million to the Company.

On September 9, 2018 Innovent Biologics (Innovent), a world-class China-based biopharmaceutical company that develops and commercializes high quality drugs, reported that its IND application for IBI188, a fully human anti-CD47 monoclonal antibody (mAb) drug candidate, has been approved by the National Medical Products Administration (NMPA, formerly known as CFDA) for clinical trials (Press release, Innovent Biologics, SEP 9, 2018, View Source [SID1234529358]). Innovent will launch several clinical trials based on this mAb drug to assess its safety and efficacy for multiple tumor types, including non-Hodgkin’s lymphoma and ovarian cancer. This is the fourth IND approval the company has received this year, including anti-CTLA-4 mAb, anti-RANKL mAb, anti-OX40 mAb and anti-CD47 mAb.

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As one of the key targets in the field of anti-tumor immunotherapy, CD47 is regarded by many experts to have the possibility of becoming the next "star" in the field of immuno-oncology following the ground-breaking success of PD1 / PD-L1 antibodies. The IND approval signals that Innovent’s discovery and development on CD47 has advanced IBI188 as a leading player for this target to enter into clinical development stage.

"Innovent, with a relentless focus on innovation and quality, has developed programs that are advancing into cutting edge drug development frontiers. We hope that through our efforts, we can advance the field of cancer treatment, provide better treatment options to increase patients’ survival rate and improve their quality of life," said Michael Yu, Founder, Chief Executive Officer and Chairman.

"Emerging data suggests that CD47 antibody in combination with other treatments, including anti-PD-1 monoclonal antibodies, could result in higher levels of anti-tumor efficacy. Innovent’s current rich pipeline will allow multiple drug combinations with IBI188 creating many opportunities to achieve breakthroughs in cancer treatment to meet more unmet patient needs in the future," said Dr. Kerry Blanchard, Chief Scientific Officer of Innovent.

CD47 is one of the most important targets in the field of immuno-oncology. The development of anti-CD47 monoclonal antibody has recently attracted much attention. Innovent will be among one of a few companies pursuing the development of an anti-CD47 antibody in the early clinical stage.

About IBI188

IBI188 is an anti-CD47 IgG4 monoclonal antibody developed by Innovent with independent intellectual property rights. Both in vitro and in vivo experiments showed that IBI188 can bind to the CD47 antigen on the surface of tumor cells, block the CD47-SIRPα signaling pathway, inhibit the "Don’t Eat Me" signal, and promote the phagocytosis of tumor cells by macrophages, thereby exerting an anti-tumor effect. It has stronger receptor blocking ability than similar drugs. Innovent will launch several clinical trials to assess its safety and efficacy for multiple tumor types, including non-Hodgkin’s lymphoma and ovarian cancer.

On September 9, 2018. Xspray Pharma reported positive data from a clinical bioequivalence study with the company’s lead product candidate HyNap-Dasa (Press release, Xspray, SEP 9, 2018, View Source [SID1234649534]). The study results confirmed its primary aim to show bioequivalence of an optimized formulation of HyNap-Dasa compared to Sprycel. The data will be instrumental in the design of the planned registration study for an ANDA application.
The completed clinical Phase I study examined HyNap-Dasa’s bioavailability compared to the dasatinib cancer drug, currently marketed as Sprycel for the treatment of chronic myeloid leukemia (CML). In the study, bioavailability of two different tablet formulations of HyNap-Dasa was tested in comparison with Sprycel tablets in 16 healthy subjects. The results are very positive and confirm the validity of Xspray’s patented formulation technology. The planned studies required to take HyNap-Dasa to final registration studies will now be performed as planned. The results also strengthen the potential for additional product candidates in the pipeline being developed with the same technology to reach the market.

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"I am happy to see that the data so strongly confirm our technology. The outcome of this study represents an important milestone for Xspray Pharma as it means that we now can initiate the preparation of the pivotal phase of the clinical program, taking us closer to a commercial launch of HyNap-Dasa. Furthermore, the results pave the way also for additional product candidates in our pipeline. It signifies a new and important step in our development as a company" said Per Andersson, CEO of Xspray Pharma.

The clinical results in summary:

The study compared the pharmacokinetic parameters Cmax and AUC for the originator product Sprycel and two different HyNap tablet formulations of dasatinib. Sixteen healthy volunteers received single doses of each product in a cross-over design. Although this study was not powered to demonstrate formal bioequivalence, an analysis of preliminary data indicate that bioequivalence with Sprycel was achieved for one of the HyNap formulations. The results demonstrate a high likelihood that formal bioequivalence will be achieved in an adequately powered study.

Sprycel is a registered trademark of Bristol-Myers Squibb.

On September 7, 2018 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, reported that the first patient has been dosed in its Phase 1 clinical trial of COM701, a first-in-class cancer immunotherapy antibody targeting PVRIG (Press release, Compugen, SEP 7, 2018, View Source [SID1234529393]). PVRIG is a novel immune checkpoint identified by Compugen using its computational discovery capabilities.

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"Dosing the first patient with COM701, a first-in-class drug opportunity targeting a novel immune checkpoint we identified with our computational predictive platform, is a landmark event for us. We look forward to clinically testing it," stated Anat Cohen-Dayag, Ph.D., Compugen’s President and CEO. "It also serves as a proof of concept for our discovery capabilities and marks Compugen as a leader in the field of computational discovery. We will continue leveraging this core competency in expanding our therapeutic pipeline and achieving our corporate and business goals."

Drew W. Rasco, M.D., Associate Director of Clinical Research at the START Center for Cancer Care and a Principal Investigator in the Phase 1 COM701 study, said, "Immunotherapy has revolutionized the landscape for oncology treatments by providing a new treatment option leading to lasting benefits for patients. Yet, response rates vary greatly across different cancer indications, leaving a significant unmet medical need for many patients and a continuing challenge to discover new biological pathways that can result in the development of new cancer immunotherapies for non-responsive and refractory patients. COM701 preclinical data suggest that the newly-discovered PVRIG pathway may be a dominant pathway in certain cancer subpopulations, including those that are unresponsive to PD‑1 or PDL-1 inhibitors. As such, it is important to evaluate COM701 in clinical trials with these patient populations who have exhausted available standard therapy."

Henry Adewoye, M.D., Chief Medical Officer of Compugen, said, "COM701 is a promising and differentiated asset in the crowded landscape of immuno-oncology trials. Our clinical and biomarker strategy for testing COM701 is premised on a robust biological rationale which suggests that targeting PVRIG may be necessary to induce a sufficient anti-tumor immune response in cancer patient subpopulations where both the PVRIG and TIGIT pathways are operative, thereby addressing the high unmet need of relapsed and refractory disease following treatment with existing immunotherapies. We look forward to exploring the full clinical potential of COM701."

This Phase 1 open-label clinical trial is designed to assess the safety and tolerability of administering escalating doses of COM701 monotherapy as well as combination administration with a PD-1 inhibitor in patients with advanced solid tumors. Additionally, the trial will evaluate evidence of preliminary antitumor activity of COM701 as a monotherapy as well as in combination with a PD-1 inhibitor in patients with selected tumor types, including non-small cell lung cancer, ovarian cancer, breast cancer and endometrial cancer. The study will be conducted in multiple leading oncology clinical centers in the United States, which are expected to enroll approximately 140 patients. Additional information will be available shortly at www.clinicaltrials.gov.

About COM701
COM701 is a humanized hybridoma antibody that binds with high affinity to PVRIG, a novel B7/CD28-like immune checkpoint target candidate discovered by Compugen, blocking its interaction with its ligand, PVRL2. Blockade of PVRIG by COM701 has demonstrated potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate anti-tumor immune responses. In addition, COM701 combined with antagonist anti-PD-1 antibodies has demonstrated synergistic effects on human T cell stimulation, indicating the potential of these combinations to further enhance immune response against tumors.

Preclinical data for COM701 suggest that PVRIG may be a dominant checkpoint in diverse patient populations with tumors that express elevated PVRL2 as compared to expression of the TIGIT ligand PVR. This include patients with breast, endometrial, and ovarian cancers. In addition, expression studies show that PVRIG and TIGIT, and their respective ligands, are expressed in a broad variety of tumor types, such as those noted above, as well as lung, kidney, and head & neck cancers. In these tumors the blockade of both TIGIT and PVRIG may be required to sufficiently stimulate an anti-tumor immune response, with or without additional PD-1 pathway blockade.