On November 13, 2018 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, reported updated clinical and biomarker data from ongoing Phase 1/1b studies of its lead programs, CPI-444 and CPI-006 (Press release, Corvus Pharmaceuticals, NOV 13, 2018, View Source [SID1234531349]). Updated results from its Phase 1/1b clinical trial of CPI-444 in patients with treatment-refractory renal cell carcinoma (RCC) demonstrated an overall survival (OS) of 88 percent at more than 20 months follow-up with CPI-444 administered in combination with atezolizumab. The clinical data were presented in an oral session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in Washington, D.C., by Lawrence Fong, M.D., study investigator and leader of the Cancer Immunotherapy Program at the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center.

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Additionally, CPI-444 biomarker data from the Phase 1/1b study showing that expression of a novel adenosine gene signature was significantly associated with tumor regression were presented both in the oral presentation and in a poster session at the SITC (Free SITC Whitepaper) meeting. Early clinical data from an ongoing Phase 1/1b study evaluating CPI-006 as a monotherapy showing evidence of immune activation of B cells were presented in a poster session.

CPI-444, Corvus’ lead product candidate, is a selective and potent inhibitor of the adenosine A2A receptor. It is currently being evaluated in Phase 1/1b and 1b/2 clinical trials in patients with various solid tumors as a monotherapy and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody. CPI-006 is a humanized monoclonal antibody directed against CD73. It is currently being evaluated in a Phase 1/1b three-arm clinical trial in patients with a variety of solid tumors as a monotherapy, in combination with CPI-444, and in combination with pembrolizumab, an anti-PD-1 antibody.

"The newest data on our two lead programs further establish a promising foundation for the application of adenosine blockade in cancer therapy," said Richard A. Miller, M.D., an oncologist and co-founder, president and chief executive officer of Corvus. "The longer-term follow-up data from our Phase 1/1b study of CPI-444 showed objective tumor responses and prolonged survival in a larger group of patients with treatment-refractory RCC, which is highly encouraging given such advanced disease."

He added, "With this study, we also discovered an adenosine gene signature that can be obtained from tumor biopsies and potentially could be used as a predictive biomarker for patient selection. This signature is expected to be an important factor as we design our CPI-444 pivotal trials. Furthermore, the biomarker and clinical data in anti-PD-(L)1 resistant, refractory patients enhance our understanding of the tumor biology. By blocking adenosine in the tumor microenvironment from binding with the A2A receptor, CPI-444 enables anti-PD-(L)1 therapies to stimulate T cell function to attack cancer cells. The biomarker data add to our understanding of the mechanism of action, which makes combination therapy very attractive since CPI-444 appears to inhibit an important anti-PD-(L)1 resistance mechanism."

Key CPI-444 Clinical Results Presented at SITC (Free SITC Whitepaper)
Study investigator Dr. Fong presented updated efficacy and safety data at SITC (Free SITC Whitepaper) from the ongoing Phase 1/1b clinical study of CPI-444 in RCC patients with progressive disease (presentation slides available on the Corvus website in the "Publications and Presentations" section, which can be found here). Study participants had advanced refractory disease and a poor prognosis. They had been treated with a median of three prior therapies (range: 1 to 5), and approximately 72 percent had failed prior anti-PD-(L)1 therapy. For more than 60 percent of patients, the protocol treatment represented a fourth, fifth or sixth line of therapy. Data from 33 patients receiving CPI-444 as a monotherapy and 35 receiving CPI-444 in combination with atezolizumab who were evaluable for response showed:

Disease control for more than 6 months was achieved in 35 percent and 17 percent of patients receiving combination therapy and monotherapy, respectively.
For patients receiving combination therapy, 11 percent experienced a confirmed partial response (PR; as determined by RECIST criteria). Several additional patients experienced tumor regression not meeting the criteria for a PR. For patients receiving monotherapy, one patient experienced a confirmed PR, one experienced an unconfirmed PR, and several patients experienced tumor regression not meeting the PR criteria.
Responses were seen in both the combination therapy and monotherapy arms, and in patients who failed prior anti-PD-(L)1 therapy.
Progression-free survival (as assessed by RECIST criteria) was 5.9 months with combination therapy and 4.0 months with monotherapy.
OS was 88 percent at 20+ months with combination therapy and 65 percent at 16+ months with monotherapy.
Combination therapy was superior to monotherapy with respect to OS, response rate, disease control rate and progression-free survival.
Evaluation of pre- and on-treatment tumor biopsies showed a statistically significant correlation between treatment-induced CD8+ T cell infiltration in tumors and response (p<0.016).
The recently described adenosine signature showed a statistically significant correlation with tumor response and disease control rates (p<0.008).
CPI-444 continues to be well tolerated to date, with observed adverse events similar to previous reports. In the combination arm, adverse events were generally consistent with other anti-PD-L1 therapies. In the monotherapy arm, grade 3 adverse events were infrequent and reversible.
Key CPI-444 Biomarker Results Presented at SITC (Free SITC Whitepaper)
Biomarker analysis, performed on tumor tissue from biopsies of 30 RCC patients treated with monotherapy or combination therapy in the ongoing Phase 1/1b study of CPI-444, showed:

Expression of the adenosine gene signature in pre-treatment tumor biopsies was significantly associated with tumor response to treatment with CPI-444 (p<0.008).
The adenosine gene signature identified a group of chemokines and cytokines that are associated with myeloid-derived suppression.
Adenosine induces the production of these chemokines and cytokines, which inhibit anti-tumor immunity. CPI-444 blocks the production of these substances.
"Our other lead program, CPI-006, is different from other previously described anti-CD73 antibodies that we are aware of," said Joseph J. Buggy, Ph.D., co-founder and executive vice president of research of Corvus. "Early clinical data from our Phase 1/1b trial presented at SITC (Free SITC Whitepaper) showed that CPI-006 inhibited CD73 enzymatic activity and stimulated intracellular signaling to activate B cells, which appears to cause the migration of lymphocytes to lymphoid tissues. This activity is independent of adenosine and could be important in stimulating anti-tumor immunity."

Key CPI-006 Clinical Results Presented at SITC (Free SITC Whitepaper)
Initial data from an ongoing Phase 1/1b clinical trial of CPI-006 administered as a monotherapy or as combination therapy in patients with various cancers who have failed standard therapies were presented at SITC (Free SITC Whitepaper). Results from nine patients who received ascending doses of CPI-006 (1, 3 and 6 mg/kg; N=3 at each dose) showed that CPI-006:

Targeted a novel epitope on CD73
Blocked production of adenosine by inhibiting the enzymatic active site of CD73
Activated peripheral blood B cells leading to increased expression of CD69 independent of adenosine
Affected B lymphocyte trafficking as shown by transient decreases of circulating B cells
Was well tolerated at the doses evaluated with no dose-limiting toxicities
In this study, dose escalation continues with CPI-006 as a monotherapy and in combination with the adenosine A2A receptor antagonist CPI-444.

About CPI-444
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic.

About CPI-006
CPI-006 is a potent humanized monoclonal antibody that reacts with the active site of CD73, blocking the conversion of AMP to adenosine. In vitro studies of CPI-006 have shown it is capable of substantially inhibiting the production of adenosine by blocking the CD73 enzyme. Clinical study results have indicated that CPI-006 has also stimulated activation of lymphoid cells in an adenosine-independent manner.

On November 13, 2018 Kleo Pharmaceuticals Inc., an immuno-oncology company pioneering a new class of bi-specific, small molecule compounds designed to emulate or enhance biologics against cancer, reported the closing of an oversubscribed $21 million Series B financing to advance its first clinical candidates through IND-enabling studies and into the clinic in 2020 (Press release, Kleo Pharmaceuticals, NOV 13, 2018, View Source [SID1234531411]). The financing was led by the company’s development partner, PeptiDream, Inc., (TOKYO:4587), with participation from current strategic investor Biohaven Pharmaceuticals Inc. (NYSE:BHVN).

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Kleo’s lead candidates are based on the Company’s modular Antibody Recruiting Molecules (ARMs) technology, which enables Kleo’s compounds to bind at one end to specific targets on cancer cells and to the body’s endogenous antibodies. This unique approach redirects the activity of any ARM-bound antibody against the cancer cells without inhibiting the antibody’s native function. In parallel, Kleo is continuing to advance its two additional immuno-oncology therapy platforms, including its Synthetic Antibody Mimics (SyAMs) and Monoclonal Antibody Therapy Enhancers (MATEs).

Douglas Manion, CEO of Kleo Pharmaceuticals, said, "Successful completion of this financing represents an important step in the translation of our groundbreaking approach into therapies that may improve patients’ lives. Having improved the modularity of our platforms and expanded the applicability of our ARMs to recruit antibodies to target cancer cells, we are now well funded to advance our first next-generation candidates into human clinical studies. We are excited to welcome our development partner PeptiDream to our community of investors, and we’re humbled by the continued support of our founding investor Biohaven."

Patrick Reid, CEO of PeptiDream, stated, "We have worked with Kleo since July 2017 and we are impressed by the scientific progress they have made in validating their technology platforms. We are enthusiastic about the robust pipeline they are building from all three of their unique immunotherapy platforms and we are very happy to be a part of it, both as a strategic partner and now as an investor. We believe Kleo’s clinical candidates represent a paradigm shift in immuno-oncology development that elegantly delivers the therapeutic power of highly complex bi-specific antibodies, but in a more simple, less costly, and potentially more beneficial manner. When combined with PeptiDream’s robust discovery platform, we expect Kleo to generate many novel drug franchises that can bring incredible value for patients suffering from cancer."

On November 13, 2018 Helix BioPharma Corp. (TSX, FSE: "HBP"), an immuno-oncology company developing drug candidates for the prevention and treatment of cancer, reported a strategic update of its LDOS47 clinical program (Press release, Helix BioPharma, NOV 13, 2018, View Source [SID1234531459]).

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Helix’s L-DOS47 strategic development plan has two parts. The first part is to ensure L-DOS47 will be used in a well-established treatment setting, while being ready to be applied in novel therapies. For this reason, L-DOS47 clinical programs will focus primarily in a combination setting. In this plan L-DOS47 will be studied with well-established chemotherapeutics and in combination with novel immunotherapy. The Company is well advanced in carrying out the study of L-DOS47 with chemotherapy in lung cancer. The planning for combining with immunotherapies in this indication is also in progress.

In the second part of the strategic development plan, the Company will focus on expanding the utility of L-DOS47 to indications other than lung cancer. In choosing a new indication for L-DOS47, the company has considered available preclinical and clinical L-DOS47 data, consulted with key opinion leaders and considered the best strategic application of limited financial resources. To this end, the Company has recently announced the start of a new pancreatic cancer program.

As of today, the Company has completed a monotherapy study of L-DOS47 in lung cancer, with two combination studies in the same indication that are actively recruiting patients. The Company is also working diligently to prepare for regulatory filing of a new pancreatic cancer study with the United Sates Food and Drug Administration ("FDA").

The following is a status update of active studies currently taking place.

LDOS001

LDOS001 is a Phase I dose escalation study of L-DOS47 with pemetrexed and carboplatin for the first line treatment in recurrent or metastatic non-squamous non-small cell lung cancer. A total of seven (7) cohorts comprising of L-DOS47 doses at 0.59, 0.78, 1.5, 3.0, 6.0, 9.0 and 12.0 ug/kg were approved. To date, five (5) cohorts have been completed and a total of 12 patients were dosed. No dose limiting toxicity was observed. In cohort 1, one patient had a partial response (36% tumor regression). In cohort 2, three other patients had partial response (40%, 44% and 91% tumor regression) and one additional patient experienced stable disease for 13.3 months. In cohort 4, one patient had a partial response (69% tumor regression). The company expects to enroll six more patients to complete recruitment for study dosing cohorts if no dose limiting toxicity is observed.

LDOS003

LDOS003 is a phase II, open-Label, randomized study of immunoconjugate L-DOS47 in combination with vinorelbine and cisplatin versus vinorelbine and cisplatin alone in patients with lung adenocarcinoma. Regulatory and Ethics approvals to dose patients were first received from Ukraine in March and from Poland in April. While the company had planned to enroll patient shortly thereafter, the program was delayed due to financial constraints. The company has recently reprioritized its resources and expects to enroll patients in this study immediately.

LDOS006

The Company recently announced the launch of a U.S. Phase I/II study of L-DOS47 in combination with doxorubicin for the treatment of metastatic pancreatic cancer. The study will be led by Dr. Daniel Von Hoff and his team. The Company is currently completing the study protocol and related documents necessary for an investigational new drug ("IND") application to the FDA.

On November 12, 2018 UroGen Pharma Ltd. (Nasdaq:URGN), a clinical-stage biopharmaceutical company developing treatments to address unmet needs in the field of urology, with a focus on uro-oncology, reported financial results for third quarter ended September 30, 2018 and that it has completed enrollment of the UGN-101 OLYMPUS Phase 3 Trial in patients with low-grade upper tract urothelial cancer (LG UTUC) following a recent pre-New Drug Application (NDA) meeting held with the U.S. Food and Drug Administration (FDA) (Press release, UroGen Pharma, NOV 12, 2018, View Source [SID1234531211]).

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At the pre-NDA meeting, the company presented updated data from this open-label, single arm Phase 3 study. The meeting resulted in agreement on the required information for the NDA submission and suitability for NDA submission of primary endpoint (Complete Response) data for the approximately 65 patients enrolled to date.

UroGen plans to present the topline data in January 2019, with the full dataset expected at a medical meeting in the second quarter of 2019.

"We are pleased by the FDA’s support for UGN-101 and recognition of the potential clinical benefit that UGN-101 presents for LG UTUC as a potentially organ-sparing, non-invasive therapy for this disease," said Ron Bentsur, Chief Executive Officer of UroGen. "We are excited about the progress that we continue to make across our clinical pipeline and look forward to collaborating with the FDA to bring this potentially transformative therapy to patients with LG UTUC."

Breakthrough Therapy Designation (BTD) was granted by the FDA for UGN1-101 for the treatment of LG UTUC in October 2018. UroGen remains on track to initiate the UGN-101 Rolling NDA Submission to the FDA in Q4 2018 and complete the submission in Q2 2019, with potential approval expected in 2019.

Additional Highlights and Upcoming Milestones

UGN-102 Clinical Development:
UroGen is enrolling patients as part of its Phase 2b single-arm, open-label, multi-center trial designed to assess the efficacy and safety of UGN-102 (mitomycin gel) for intravesical instillation as a potential first-line chemoablation agent in the treatment of patients with LG Non-Muscle Invasive Bladder Cancer (NMIBC) at risk for recurrence.
Initial data from the trial is expected in 1H 2019.
Similar to LG UTUC, there are currently no drugs approved by the FDA as first-line treatment for NMIBC, and only three drugs have been approved by the FDA, all as adjuvant treatments, following TURBT (transurethral resection of bladder tumor).
UGN-102 represents a very substantial opportunity in UroGen’s pipeline with the potential to initially address up to approximately 85,000 patients for whom TURBT is no longer effective.1
Advancing the Potential of the RTGel Platform:
Allergan continues to enroll patients in its Phase 2 trial of BotuGel, UroGen’s RTGel in combination with BOTOX2, for the treatment of overactive bladder. This clinical trial, if successful, has the potential to demonstrate the broad applicability of the RTGel platform beyond uro-oncology. Phase 2 data is expected in 2019.
Corporate Developments:
UroGen strengthened its leadership team with the appointment of Jones "Woody" Bryan, Ph.D., as Senior Vice President, Business Development. Dr. Bryan is a seasoned industry veteran who brings over 25 years of industry experience. He is focused on the integration of corporate strategy and business development to assess potential partnerships, both inbound and outbound, and bolster UroGen’s product portfolio.
Third Quarter 2018 Financial Results

As of September 30, 2018, cash and cash equivalents totaled $109.5 million.
Research and development expenses for the nine months ended September 30, 2018 were $25.5 million, including non-cash share-based compensation expense of $9.1 million. Research and development expenses for the three months ended September 30, 2018 were $9.6 million, including non-cash share-based compensation expense of $3.8 million.
General and administrative expenses for the nine months ended September 30, 2018 were $27.0 million, including non-cash share-based compensation expense of $12.7 million. General and administrative expenses for the three months ended September 30, 2018 were $10.7 million, including non-cash share-based compensation expense of $5.7 million.
The Company reported a net loss of $51.9 million, or basic and diluted net loss per ordinary share of $3.30, for the nine months ended September 30, 2018. The Company reported a net loss of $20.5 million, or basic and diluted net loss per ordinary share of $1.28, for the three months ended September 30, 2018.
Conference Call & Webcast Information

Members of UroGen’s management team will host a live conference call and webcast today at 8:30 a.m. Eastern Time to review the Company’s financial results and provide a general business update. Due to observance of the Veteran’s Day holiday in the United States on November 12, 2018, UroGen’s corresponding 6-K will be filed with the Securities and Exchange Commission (SEC) before market on November 13, 2018.

The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call (888) 771-4371 (U.S.) or (847) 585-4405 (International) to listen to the live conference call. The conference ID number for the live call will be 47697839. An archive of the webcast will be available for two weeks on the Company’s website.

On November 12, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on the development of novel cellular immunotherapies, reported that the Company will host an investor event to discuss its efforts in solid tumors on Monday November 19, 2018, from 8:30 a.m. to 10:00 a.m. ET in New York City (Press release, Unum Therapeutics, NOV 12, 2018, View Sourcenews-releases/news-release-details/unum-therapeutics-host-investor-event-its-efforts-realize" target="_blank" title="View Sourcenews-releases/news-release-details/unum-therapeutics-host-investor-event-its-efforts-realize" rel="nofollow">View Source [SID1234531331]).

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The event will feature guest speaker Charles S. Fuchs, MD, MPH, Director of the Yale Cancer Center, who will discuss the challenges and opportunities in HER2 malignancies. In addition, the Company will discuss the unmet need, clinical validation of ACTR707 and design of the ATTCK-34-01 Phase I trial using ACTR707 in combination with trastuzumab to target HER2-positive advanced cancers. The Company also will provide more details on the new BOXR platform to support its growing efforts in solid tumors.

To join the live webcast, please visit the investor relations section of the Unum Therapeutics website at View Source at least 10 minutes before the event begins.