On May 13, 2020 Brickell Biotech, Inc. ("Brickell") (Nasdaq: BBI), a clinical-stage pharmaceutical company focused on developing innovative and differentiated prescription therapeutics for the treatment of debilitating skin diseases, reported financial results for the first quarter ended March 31, 2020 and provided a corporate update (Press release, Vical, MAY 13, 2020, View Source [SID1234557902]).

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"Brickell has continued to make progress during the first quarter of 2020, and we remain committed to advancing sofpironium bromide into Phase 3 clinical studies in the U.S.," commented Robert Brown, Chief Executive Officer of Brickell. "As we continue to prepare for the initiation of our pivotal studies, we are encouraged by the top-line results of our recently completed Phase 3 long-term safety study. Furthermore, the Japanese Phase 3 pivotal study data that we expect to be presented by our Asian development partner, Kaken Pharmaceutical Co. Ltd. ("Kaken"), next month further strengthens our enthusiasm of sofpironium bromide’s potential to be a best-in-class therapy for hyperhidrosis."

Business and Recent Developments

Today, Brickell announced that, based on a preliminary review of the top-line results from the 12-month Phase 3 open-label long-term safety study, in 300 subjects >9 years old with primary axillary hyperhidrosis, sofpironium bromide gel, 5% and 15% was safe and generally well tolerated, which was consistent with the earlier Phase 2 clinical trial results. No treatment-related serious adverse events were observed.

On March 4, 2020, Brickell announced that positive results from Kaken’s Phase 3 pivotal study of topically applied sofpironium bromide gel, 5% in Japanese subjects with primary axillary hyperhidrosis were selected for oral presentation at the Late-Breaking Research Program of the American Academy of Dermatology ("AAD") Annual Meeting. Due to concerns related to COVID-19, the AAD canceled the conference and it is now rescheduled to be a virtual forum on June 12, 2020. The presentation will include details of the efficacy and safety results from Kaken’s Phase 3 pivotal study of sofpironium bromide gel.

On February 20, 2020, Brickell announced that positive results from its Phase 2b study with sofpironium bromide in patients with primary axillary hyperhidrosis were published in the peer-reviewed Journal of the American Academy of Dermatology ("JAAD"). In this Phase 2b dose-finding study, sofpironium bromide elicited clinically meaningful and statistically significant sustained reductions in sweating severity and was well tolerated. The paper, entitled "Efficacy and Safety of Topical Sofpironium Bromide Gel for the Treatment of Axillary Hyperhidrosis: A Phase II, Randomized, Controlled, Double-Blinded Trial," is available online (View Source) and will be published in volume 82, Issue 6 (2020) pp.1320-1327 in the June 2020 print edition of JAAD.

On February 18, 2020, Brickell announced that Brickell, Bodor Laboratories, Inc. and Dr. Nicholas S. Bodor entered into a binding settlement agreement and an amended license agreement, concluding all litigation related thereto and allowing Brickell to continue development of sofpironium bromide for the treatment of hyperhidrosis.

On February 18, 2020, Brickell announced entry into a purchase agreement with Lincoln Park Capital Fund, LLC ("LPC"), a long-only Chicago-based institutional investor, whereby LPC purchased $2.0 million in Brickell common stock and warrants. Additionally, Brickell and LPC entered into a separate purchase agreement whereby Brickell, for up to a 36-month period, will have the right, in its sole discretion subject to satisfaction of certain conditions, to sell up to an additional $28 million of its common stock to LPC. This agreement is intended to augment the various potential sources of capital the Company may have access to as Brickell develops sofpironium bromide for the treatment of axillary hyperhidrosis.

On January 19, 2020, Brickell presented the results from pharmacokinetics and long-term safety extension trials with sofpironium bromide gel, 15% in pediatric patients (ages 9 to <17) with primary axillary hyperhidrosis at the Dermatology, Aesthetic & Surgical Conference. Sofpironium bromide was safe and well-tolerated over 24 weeks of treatment in this clinical trial.

On January 10, 2020, Brickell announced that Kaken submitted a new drug application for approval with the Pharmaceuticals and Medical Devices Agency in Japan for the manufacturing and marketing of sofpironium bromide gel for primary axillary hyperhidrosis.
Financial Results
Cash, cash equivalents, and marketable securities were $7.1 million as of March 31, 2020 compared to $11.7 million as of December 31, 2019. In addition, Brickell has prepaid $4.6 million to third-party clinical research organizations in anticipation of commencing Phase 3 pivotal clinical trials of sofpironium bromide in the U.S.

Revenue was $1.0 million for the first quarter of 2020 compared to $3.5 million for the first quarter of 2019. The decrease in revenue recognized was attributable to the Phase 3 long-term safety study of sofpironium bromide gel and other ancillary studies that were ongoing in 2019 but were concluded or winding down by the first quarter of 2020. Conducting these studies is the basis for revenue recognition for a $15.6 million R&D payment that was received from Kaken in the second quarter of 2018.

Research and development expenses were $2.7 million for the first quarter of 2020 compared to $6.0 million for the first quarter of 2019. This decrease was primarily due to a decrease in clinical study and other related regulatory and administrative costs of the Phase 3 long-term safety study of sofpironium bromide gel and other ancillary studies that were ongoing in 2019, but were concluded or winding down by the first quarter of 2020.

General and administrative expenses were $2.5 million for the first quarter of 2020 compared to $2.1 million for the first quarter of 2019. This increase was primarily due to $0.3 million in higher fees for directors’ and officers’ liability insurance as a public company.
Brickell’s net loss was $4.1 million for the first quarter of 2020 compared to $4.6 million for the first quarter of 2019.
Conference Call and Webcast Information
Brickell’s management will host a conference call today at 4:30 p.m. ET to discuss the financial results and recent corporate developments. The dial-in number for the conference call is 1-855-327-6837 for domestic participants and 1-631-891-4304 for international participants, with Conference ID #10009475. A live webcast of the conference call can be accessed through the "Investors" tab on the Brickell Biotech website at View Source A replay will be available on this website shortly after conclusion of the event for 90 days.
About Sofpironium Bromide
Sofpironium bromide is a proprietary new molecular entity that belongs to a class of medications called anticholinergics. Anticholinergics block the action of acetylcholine, a chemical that transmits signals within the nervous system that are responsible for a range of bodily functions, including activation of the sweat glands. Sofpironium bromide was retrometabolically designed. Retrometabolic drugs are designed to exert their action topically and are potentially rapidly metabolized into a less active metabolite once absorbed into the blood. This proposed mechanism of action may allow for highly effective doses to be used while limiting systemic side effects. Sofpironium bromide was discovered at Bodor Laboratories, Inc. by Dr. Nicholas Bodor D.Sc., d.h.c. (multi), HoF, Graduate Research Professor Emeritus, University of Florida. Sofpironium bromide is not approved for use in any country at this time.

About Hyperhidrosis

Hyperhidrosis is a life-altering medical condition where a person sweats more than the body requires to regulate its temperature. More than 15 million people, or 4.8% of the population of the United States, and more than 16 million people, or 12.76% of the population in Japan, are believed to suffer from hyperhidrosis1,2. Primary axillary (underarm) hyperhidrosis is the targeted first indication for sofpironium bromide and is the most common site of occurrence of hyperhidrosis, affecting an estimated 65% of patients with hyperhidrosis in the United States or 10 million individuals and an estimated 45% of patients with hyperhidrosis in Japan or 7.2 million individuals1,2. Additional information can be found on the International Hyperhidrosis Society website: View Source

On May 13, 2020 I-Mab (NASDAQ: IMAB), a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel or highly differentiated biologics to treat diseases with significant unmet medical needs, reported that the first patient has been dosed in a Phase 1/2 clinical study in China to evaluate I-Mab’s proprietary CD73 antibody TJD5, also known as TJ004309, in patients with advanced solid tumors (CTR20200445; NCT04322006) (Press release, I-Mab Biopharma, MAY 13, 2020, View Source [SID1234557901]).

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"It’s exciting news that the TJD5 study has been initiated in China. TJD5 represents a promising novel compound targeting the cancer microenvironment. This could bring new hopes to the patients if safety and efficacy could be demonstrated," said Professor Yi-Long Wu, Tenured Professor of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, South China University of Technology, Chair of Chinese Thoracic Oncology Group.

This Phase 1/2 study is a multicenter, open-label, dose escalation and cohort expansion study, which will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of TJD5, and determine a recommended dose for further clinical studies of its efficacy and safety as a single agent and in combination with standard dose of toripalimab (TUOYI ) in patients with advanced or metastatic cancers who are refractory to or intolerant of all available therapies.

"We are pleased to advance TJD5 into the clinical study in China and are committed to realizing the potential of TJD5 as a next-generation immuno-oncology agent," said Dr. Joan Shen, M.D., Ph.D., CEO of I-Mab. "We have been able to accelerate the Phase 1/2 trial in China by leveraging data from the ongoing Phase 1 clinical study of TJD5 in the United States, which is a testament to our global clinical development capabilities and well-executed pipeline strategies."

"The low response rates to PD-1/PD-L1 inhibitor treatments in cancer patients remain a significant unmet clinical need. As CD73 is widely expressed in various cancers, we hope the combination therapy of TJD5 with toripalimab could provide a potential new transformational treatment option for patients in need," Dr. Shen added.

I-Mab entered into a research collaboration with Junshi Biosciences (HKEX:01877) in September 2019 to evaluate TJD5 in combination with toripalimab (TUOYI) for the treatment of patients with cancers in China.

About TJD5 (TJ004309)

TJD5 is a differentiated, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine. Adenosine binds adenosine A2A and A2B receptors on immune cells and inhibits immune responses directed against tumors. TJD5 is expected to suppress the immunosuppressive tumor micro-environment and to work in concert with other cancer therapies such as PD-1 and PD-L1 antibodies. TJD5 exerts anti-tumor activities through a unique intra-dimerization mechanism to completely inhibit the activity of the targeted enzyme as evident in preclinical studies.

TJD5 is also in a Phase 1 clinical trial in the US to assess the tolerability and preliminary efficacy as a single agent and in combination with atezolizumab (TECENTRIQ), a PD-L1 antibody marketed by Roche, in patients with advanced solid tumors.

On May 13, 2020 The ECOG-ACRIN Cancer Research Group reported that the final results of the randomized phase two trial E3311 will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, to occur virtually from May 29-31 (Press release, ECOG-ACRIN, MAY 13, 2020, View Source [SID1234557899]). The trial, conducted in patients undergoing transoral robotic surgery (TORS), tested reduced postoperative radiation therapy in patients with human papillomavirus-associated oropharynx squamous cell carcinoma at intermediate risk for recurrence. ASCO (Free ASCO Whitepaper) is highlighting the importance of the positive results by making it the first presentation in its Head and Neck Oral Abstract Session (Abstract 6500). The ECOG-ACRIN Cancer Research Group designed and conducted the trial with funding from the National Cancer Institute, part of the National Institutes of Health.

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"Transoral resection followed by low-dose radiation is safe in patients with intermediate-risk locally advanced oropharynx cancer, with very good oncologic outcome," said lead investigator Robert L. Ferris, MD, PhD, director, UPMC Hillman Cancer Center in Pittsburgh and a surgical oncologist specializing in head and neck cancer (pictured). "These results present a promising deintensification approach."

Most pharynx cancers caused by HPV have a very good outcome, and the cancer does not return or spread to other parts of the body after treatment. Dr. Ferris and colleagues sought to prove the benefits of using tumor pathologic features, obtained in specimens collected at surgery, to determine patients’ risk of recurrence–low, intermediate or high. In particular, they sought to more clearly define the prognostic and predictive role of traditional pathologic biomarkers such as extensive nodal or extranodal disease, to give the right amount of postoperative treatment for each risk group.

Patients at low risk were observed. Patients at intermediate risk were randomized to two arms of radiation alone, both at doses lower (50Gy or 60Gy) than usual (60-66Gy). At the time the trial opened in 2013, the optimal dose of radiation therapy was not defined. Patients at high risk were assigned to usual radiation therapy plus chemotherapy.

"Study E3311 met its primary endpoint," said Dr. Ferris. "For intermediate risk patients–those with uninvolved surgical margins, less than five involved nodes, and less than 1mm extranodal extension–reduced-dose postoperative radiation therapy without chemotherapy appears sufficient. In our study, this group had better outcomes than the group on usual high-dose radiation plus chemotherapy, showing that our patient stratification identified low and intermediate risk patients well, preserving patients’ throat function and sparing them unnecessary short- and long-term toxicities."

For patients with low-risk disease, two-year progression-free survival (PFS) was favorable without postoperative therapy (observation alone). All arms had two-year survival rates above 90% and there was no excess of local recurrences with reduction in radiation or chemotherapy (Arms B and C). Risk stratification appeared to appropriately select patients for observation (Arm A).

The overall intent of E3311 was to gather essential data for the design of a future, randomized phase three trial. The primary endpoint was to determine the feasibility and oncologic efficacy of a prospective multi-institutional study of TORS for HPV+ oropharynx cancer followed by risk-adjusted adjuvant therapy. The primary endpoint was two-year progression-free survival in patients determined to be at intermediate risk after surgical excision.

"The tissue samples and imaging studies collected in the course of this trial are a rich resource for studying the biology of intermediate- and high-risk disease, in work that is ongoing," said ECOG-ACRIN Head and Neck Committee Chair, Barbara A. Burtness, MD, Professor of Medicine, and Co-Leader, Developmental Therapeutics Program, Yale Cancer Center and Yale School of Medicine (pictured). "ECOG-ACRIN plans to pursue the current data with a randomized phase three trial of TORS-based treatment deintensification compared with conventional chemoradiation."

A lump in the neck and a sore throat are the most common signs of oropharynx cancer, a disease in which cancer cells form in the tissues of the oropharynx–the middle part of the throat (pharynx), at the base of the tongue and tonsils. About 60% of oropharynx cancers are associated with HPV infection. The incidence has been increasing in recent years, especially in individuals under the age of 45. This change is attributed to the increasing prevalence of HPV infection in developed countries, the practice of oral sex, and the rising number of sexual partners.

While surgeons and patients widely favor the organ-preservation approach of transoral robotic surgery, there remain serious concerns about both short- and long-term toxicities associated with chemotherapy. Besides, given the potential long-term consequences of radiation therapy for a younger population, re-evaluation of adjuvant treatment intensity is needed.

On May 13, 2020 An Upstate Medical University urology professor reported that it has been awarded a grant from the Department of Defense (DOD) to continue and advance his research on kidney cancer (Press release, SUNY Upstate, MAY 13, 2020, View Source [SID1234557898]).

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The grant will support work by Mehdi Mollapour, PhD, vice chair for translational research for the department of urology, and his lab as it continues a decade-long research project into understanding kidney cancer biology and to develop novel therapeutic strategies to treat patients. Mollapour, professor of urology, molecular biology and biochemistry, is also the director of kidney cancer biology at Upstate.

His work, published in high-impact-factor journals (Dushukyan et al, 2017, Cell Reports & Oberoi et al, Proceedings of the National Academy of Sciences, 2016) identified a prosurvival role for PP5 protein in kidney cancer. Mollapour’s lab is currently funded by several grants from the National Institutes of Health and the National Cancer Institute. He applied for this DOD grant last fall and was notified of the award this spring.

"It’s always exciting when any grant is funded," he said. "From small amounts to big amounts, to have the funds to be able to continue our work and pay students and pay researchers is exciting."

About 74,000 Americans will be diagnosed with kidney cancer in 2020, according to the American Cancer Society. The disease is more common in men and kills nearly 15,000 people in the U.S. each year, according to the ACS.

In the application for the DOD grant, Mollapour’s lab cites a higher risk for developing kidney cancer among military families because of environmental exposures. The application also talks about what a difficult disease it can be to treat, highlighting the need to seek biomarkers for early detection and new therapies like those being developed in Mollapour’s lab. Traditional radiation and chemotherapies are ineffective in patients with kidney cancer and when presenting with large or locally advanced tumors, about 50 percent develop metastatic disease, for whom the five-year survival rate is less than 20 percent, according to the application.

The most recent grant – Mollapour’s first from the DOD – will propel the lab’s work and continue to open doors for additional funding.

"The grant allows us to better understand this disease and new ways of treating it. Naturally, data generated here will enable us to obtain further funding," he said. The $400,000 grant will support research staff, including students, working in the lab for two years. He and his staff are actively applying for additional funding from the National Institutes of Health.

Mollapour credits the work of everyone in his lab for obtaining this grant. After learning the good news about the DOD funding, Mollapour said he does what he always does when he is notified of new grant funding – he calls Upstate Chair of Urology Gennady Bratslavsky, MD, on the phone and plays the song "We Are The Champions," by Queen over the phone.

"When he hears that he knows what happened," Mollapour said laughing. "We have a secret code and Bratslavsky gets equally excited because he appreciates the importance of research and that is why he is fully committed in supporting research."

Mollapour and Bratslavsky worked together before coming to Upstate.

"Dr. Mollapour is a brilliant scientist and I take great pride in being able to recruit him from the National Cancer Institute where we both worked in urologic oncology studying kidney cancer," Bratslavsky said. "I respect Dr. Mollapour’s talent in research, his perseverance and his ability to be a mentor for many of my students and residents."

Mollapour said this grant is exciting and important because of its direct connection to patient care and its potential to extend the lives of kidney cancer patients.

"I know whatever we are going to do in terms of research will directly impact the kidney cancer patient," he said. "This is not one of those types of research that is 10 steps away from helping the patient. This is so gratifying and very exciting. The patient is always on my mind. It might be cliché but I really think we will help the patients with this. We are going to make it happen one way or another."

On May 13, 2020 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported updated safety and initial efficacy data contained in an abstract scheduled as an oral presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held May 29–31, 2020 (Press release, Arvinas, MAY 13, 2020, View Source [SID1234557897]). The presentation will share updated data from the dose escalation portion of Arvinas’ Phase 1/2 clinical trial of ARV-110 in men with metastatic castration-resistant prostate cancer. The abstract describes two patients with ongoing confirmed prostate-specific antigen (PSA) responses, including one with an unconfirmed partial tumor response.

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"We are thrilled to present the first evidence that our PROTAC protein degrader, ARV-110, can provide clinical efficacy," said John Houston, Ph.D., President and Chief Executive Officer at Arvinas. "This is a significant milestone for our technology platform and for the field of targeted protein degradation."

"While still early, we are pleased to see a safety profile to date for ARV-110 that continues to support dose escalation," added Ron Peck, M.D., Chief Medical Officer at Arvinas. "Our trial of ARV-110 has enrolled a particularly heavily pre-treated population of patients who have exhausted most available treatment options. Most patients received both enzalutamide and abiraterone as well as prior chemotherapy. Despite this, ARV-110 demonstrated the first evidence of antitumor activity in this difficult-to-treat patient population."

The presentation will include data collected since the abstract submission date. Dose escalation continues, with enrollment initiated above the previously disclosed daily dose of 280 milligrams.

Abstract details are as follows:
Presentation Title: First-in-human phase I study of ARV-110, an androgen receptor PROTAC degrader in patients with metastatic castrate-resistant prostate cancer following enzalutamide and/or abiraterone
Abstract Number: 3500
Session Type: Oral Abstract Session
Session Track: Development Therapeutics – Molecularly Targeted Agents and Tumor Biology

For a copy of the abstract, please visit ASCO (Free ASCO Whitepaper)’s official website.

About ARV-110
ARV-110 is an orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About Metastatic Castration-Resistant Prostate Cancer (mCRPC)
In the United States, prostate cancer is both the second most prevalent cancer in men and the second leading cause of cancer death in men. The American Cancer Society predicts that one in nine men will be diagnosed with prostate cancer in his lifetime. Metastatic castration-resistant prostate cancer (mCRPC) is defined by disease progression despite androgen deprivation therapy and is often correlated with rising levels of prostate-specific antigen (PSA).

Current AR-targeted standard of care treatments for mCRPC are less effective in patients whose disease has increased levels of androgen production, AR gene or gene enhancer amplification, or AR point mutations. Up to 25 percent of patients do not respond to second-generation hormone therapies like abiraterone and enzalutamide, and the vast majority of responsive patients will ultimately become resistant, resulting in poor prognoses for men diagnosed with this devastating condition.