Ascentage Pharma Announces Approval for the Phase Ib/II Clinical Study of MDM2-p53 Inhibitor APG-115 in Combination with Immunotherapy for the Treatment of Patients with Advanced Liposarcoma or other Advanced Solid Tumors in China

On October 26, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has approved a Phase Ib/II study of Ascentage Pharma’s novel MDM2-p53 inhibitor APG-115 in combination with PD-1/PD-L1 inhibitors for the treatment of patients with advanced liposarcoma (LPS) or other advanced solid tumors (Press release, Ascentage Pharma, OCT 26, 2020, View Source [SID1234569072]).

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This multicenter, open-label Phase Ib/II study of the combination therapy in patients with advanced LPS or other advanced solid tumors in China comprises two stages – a Phase Ib dose-escalation study designed to evaluate the safety and tolerability of APG-115 in combination with a PD-1 inhibitor (toripalimab); and a Phase II dose-expansion study which will also assess the efficacy in the treatment of patients with TP53 wild-type MDM2-amplified LPS.

LPS is a common histologic subtype of soft issue sarcomas, accounting for around 20% of all soft tissue sarcoma incidences. MDM2 amplification is common in LPS, while TP53 wild-type LPS accounts for approximately half of all LPS cases[1]. Surgical resection is the current primary standard of care treatment for LPS, and pre/post-surgical chemotherapy, with or without radiation, are also recommended. Patients with advanced relapsed or metastatic LPS also receive systemic chemotherapy. However, according to the existing data, chemotherapy only offers limited benefits to patients with advanced LPS, with 80% LPS cases eventually relapsing[2]. Furthermore, current targeted therapies and immunotherapies for the treatment of LPS remain very limited in options and efficacy[3]. Therefore, a comprehensive understanding of the pathological characteristics of LPS and the development of novel and effective combination therapies for LPS are urgently needed.

APG-115 is an orally administered, selective, small-molecule inhibitor of the MDM2 protein. APG-115 has strong binding affinity to MDM2 and is designed to activate tumor suppression activity of p53 by blocking the MDM2-p53 protein-protein interaction. APG-115 is the first MDM2-p53 inhibitor entering clinical development in China, with multiple ongoing clinical studies in solid tumors and hematologic malignancies in China and the US.

Thus far, APG-115 as a single agent in advanced LPS has already shown promising antitumor activities. The Phase I study of APG-115 single agent demonstrated clinical activities in LPS and other tumors of the TP53 wild-type, implicating that TP53 wild-type is a potential biomarker for predicting the efficacy of APG-115 in the treatment of LPS and other tumor types. The study has observed over 10 months of sustained post-treatment response in a patient who had achieved partial response (PR), indicating the potential host immune-modulating effect of APG-115. These results paved the way for the further investigation of APG-115 as a single agent or in combinations with immunotherapies[4]. Preclinical studies have shown that APG-115 could stimulate the release of proinflammatory cytokines in T-cells, enhance the activation of CD4+ T-cells, and elevate the PD-L1 expression in various tumor cells. Also observed was that the APG-115 plus PD-1 inhibitor combination significantly bolstered the antitumor activities in multiple tumor models.

"At present, there is urgent unmet medical need in the treatment of LPS and other solid tumors globally," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As the first MDM2-p53 inhibitor entering clinical development in China, APG-115 single agent has demonstrated promising clinical utility in the treatment of advanced LPS. Meanwhile, preclinical studies of the APG-115 plus PD-1 inhibitor combination has also shown encouraging results. We will press ahead with this Phase Ib/II study of APG-115 plus immunotherapy combination in China, which hopefully will offer a new option to the treatment of LPS and other solid tumors."

Scorpion Therapeutics Launches with $108 Million to Advance Precision Oncology 2.0

On October 26, 2020 Scorpion Therapeutics, Inc., a next-generation precision oncology company, reported the closing of a $108 million Series A financing, led by Atlas Venture, Omega Funds, and Vida Ventures, with participation from Abingworth and Partners HealthCare Innovation (Press release, Scorpion Therapeutics, OCT 26, 2020, View Source [SID1234569070]). The financing will be used to advance Precision Oncology 2.0., the next wave in precision medicine, with the goal of delivering best- and first-in-class small molecule drugs that are safe and well-tolerated and that can provide deeper, more durable responses to many more people with cancer. The company was founded by a team of world-renowned drug developers and researchers in cancer biology and targeted oncology, including Gary D. Glick, Ph.D., Keith Flaherty, M.D., Gaddy Getz, Ph.D., and Liron Bar-Peled, Ph.D.

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Scorpion’s drug discovery and development engine builds on two decades of innovation in cancer genomics and integrates cutting-edge technologies across target discovery, medicinal chemistry, and translational medicine to deliver the next generation of precision oncology medicines. By developing medicines that are better able to spare healthy tissue and minimize side effects, the company aims to address cancers that are untreatable or treatment-resistant today so that precision oncology can become the norm – rather than the exception.

"Cancer is a complicated and devastating disease that continues to evade our best efforts to conquer it. Precision medicine represents a tremendous advance, with the potential to offer increased efficacy and decreased toxicity, but its promise remains unfulfilled for far too many patients," said Dr. Glick, the company’s founding president and CEO. "At Scorpion, we have assembled a world-class team to push the limits of biology, bioinformatics, and medicinal chemistry to identify and drug the most promising therapeutic targets for cancer patients. Our deep capabilities in next-generation chemistry enable us to design precision therapeutics for both new targets and those previously dismissed as undruggable. Moreover, we have assembled leaders in clinical development, with the expertise to efficiently advance our product candidates to patients. With these tools, we are building an unparalleled pipeline of small-molecule drugs to address untapped vulnerabilities in cancer and provide fresh hope to people in need."

Comprehensive tumor molecular profiling has uncovered thousands of recurrent genetic mutations now known to be important drivers of cancer. This has led to some notable therapeutic breakthroughs; however, the promise of precision oncology has not been fully exploited. First, many existing therapies have suboptimal therapeutic profiles, failing to provide maximum benefit to patients; second, many targets that are now known to be important for cancer proliferation and survival are still considered to be "undruggable" and therefore have yet to be targeted for therapy; and third, multi-omic data that may hold the key to transformative novel cancer targets has historically been too difficult to mine.

Scorpion has assembled the talent and technology to address these current limitations and developed a strategy to deliver on the full promise of precision oncology. Scorpion will focus initially on three key efforts: designing best or first-in-class drugs against known oncogenes; drugging known – but classically undruggable – cancer targets; and discovering and rapidly drugging novel targets with the potential to transform cancer treatment paradigms.

Scorpion’s lead investors noted that they were drawn to the company’s founding team, cutting-edge science, and bold vision of making precision oncology the norm rather than the exception.

"Scorpion’s delivery of Precision Oncology 2.0 is smart and systematic. Even in the midst of the COVID-19 pandemic, the company has assembled a renowned team, built a cutting edge discovery engine, and established a robust preclinical pipeline," said Paulina Hill at Omega Funds.

"Their investments in data sciences and next-generation chemistry power a discovery engine that is purpose-built to find the best drugs for proven targets, as well as exploit novel ones. We look forward to supporting the Scorpion team in their mission to change the landscape of cancer treatment," said Arjun Goyal, Co-founder and Managing Director at Vida Ventures.

"I am delighted to partner again with Gary, and like we did at IFM, help build another world-class biopharmaceutical company," said Jean-François Formela, Partner at Atlas Venture.

Pioneering founders

Scorpion’s founders and scientific advisors are pioneers in the field of cancer genomics and in the development of targeted cancer therapies.

Dr. Glick is a biotech entrepreneur, academic chemist, and immunology researcher. He previously founded Lycera, FirstWave Bio, and IFM Therapeutics. During Dr. Glick’s tenure as CEO of IFM, the company progressed three programs from ideation to clinical development and executed several major transactions. In 2017, IFM sold two cancer assets to Bristol-Myers Squibb in a deal valued over $2.3 billion and, in 2019, IFM sold its NLRP3 inhibitor program to Novartis for $1.6 billion. Dr. Glick also led the structuring and negotiation of a collaboration and option agreement with Novartis valued at over $840 million to develop inhibitors of the cGAS/STING pathway to treat inflammatory and autoimmune diseases. He currently serves as Executive Chairman of IFM.

Dr. Flaherty is director of clinical research at the Massachusetts General Hospital Cancer Center and professor of medicine at Harvard Medical School. A co-author of more than 300 papers, he led teams that made seminal discoveries about the genetics and treatment of melanoma. In 2013, Dr. Flaherty co-founded Loxo Oncology, where he served on the Board of Directors and chaired the Scientific Advisory board until its acquisition by Eli Lilly for $8 billion. He is also a co-founder of Strata Oncology, X4 Pharmaceuticals, and Apricity.

Dr. Getz is an internationally acclaimed and widely published leader in cancer genomics and directs the Cancer Genome Computational Analysis Group at the Broad Institute of MIT and Harvard, among other affiliations. He directs bioinformatics research and holds an endowed chair at the Massachusetts General Hospital Cancer Center. His lab focuses on characterizing cancer genetics and identifying key drivers of disease.

Dr. Bar-Peled is an assistant professor of medicine at Harvard Medical School and the Cancer Center at Massachusetts General Hospital. His lab has made key contributions to understanding how cells sense and respond to oxidative stress and developing small molecule inhibitors against difficult-to-drug cancer drivers.

An experienced scientific leadership team

Scorpion is led by an experienced group of drug hunters who have led the discovery, development, and commercialization of multiple oncology drugs. Joining Dr. Glick is Darrin Stuart, Ph.D. as chief scientific officer, Angel Guzman Perez, Ph.D. as head of discovery, and Erica Jackson as EVP of target biology.

Dr. Stuart previously served as executive director of cancer biology and drug discovery at Novartis, where he led or oversaw ten small-molecule oncology programs from ideation into first-in-human trials. Notably, Dr. Stuart was the project leader for the BRAFTOVI (encorafenib) program, which is now approved to treat patients with BRAFV600mut melanoma and colorectal cancer. Dr. Stuart also led an active basic research lab, which published multiple high-impact manuscripts on MAPK pathway biology and therapeutics.

Dr. Guzman-Perez joins Scorpion from Amgen’s research organization, where he served as executive director, head of medicinal chemistry, and was responsible for the small-molecule portfolio across therapeutic areas. Previously, Dr. Guzman-Perez spent 14 years at Pfizer. He has co-authored more than 50 peer-reviewed publications, been a co-inventor on more than 20 patents, and contributed to the advancement of more than 20 compounds to preclinical development.

Dr. Jackson has spent the past 20 years leading teams and mentoring scientists in oncology target validation and large and small molecule drug discovery. Prior to joining Scorpion, Erica was Senior Director of Oncology Discovery at AbbVie, where she led a cross-site team responsible for all biology aspects of drug discovery from target ID through candidate nomination. Before AbbVie, she spent two years at ORIC Pharmaceuticals, helping to move ORIC-101, a glucocorticoid receptor inhibitor, into the clinic. Erica began her industry career at Genentech, where she spent 10 years across roles of increasing responsibility in oncology discovery.

Eagle Pharmaceuticals to Discuss Third Quarter 2020 Financial Results on November 2, 2020

On October 26, 2020 Eagle Pharmaceuticals, Inc. ("Eagle" or the "Company") (Nasdaq: EGRX) reported that the Company will release its 2020 third quarter financial results on Monday, November 2, 2020, before the market opens (Press release, Eagle Pharmaceuticals, OCT 26, 2020, View Source [SID1234569068]).

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Scott Tarriff, Chief Executive Officer, and Pete Meyers, Chief Financial Officer, will host a conference call to discuss the results as follows:

Date

Monday, November 2, 2020

Time

8:30 a.m. ET

Toll free (U.S.)

866-342-8591

International

203-518-9713

Webcast (live and replay)

www.eagleus.com, under the "Investor Relations" section

A replay of the conference call will be available for one week after the call’s completion by dialing 800-934-3336 (US) or 402-220-1148 (International) and entering conference call ID EGRXQ320. The webcast will be archived for 30 days at the aforementioned URL.

Medpace Holdings, Inc. Reports Third Quarter 2020 Results

On October 26, 2020 Medpace Holdings, Inc. (Nasdaq: MEDP) ("Medpace") reported financial results for the third quarter ended September 30, 2020 (Press release, Medpace, OCT 26, 2020, View Source [SID1234569067]).

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Third Quarter 2020 Financial Results

Revenue for the three months ended September 30, 2020 increased 6.5% to $230.4 million, compared to $216.2 million for the comparable prior-year period. On a constant currency organic basis, revenue for the third quarter of 2020 increased 5.8% compared to the third quarter of 2019.

Backlog as of September 30, 2020 grew 16.7% to $1.4 billion from $1.2 billion as of September 30, 2019. Net new business awards were $315.4 million, representing a net book-to-bill ratio of 1.37x for the third quarter of 2020, as compared to $285.4 million for the comparable prior-year period. The Company calculates the net book-to-bill ratio by dividing net new business awards by revenue.

For the third quarter of 2020, total direct costs were $156.2 million, compared to total direct costs of $152.1 million in the third quarter of 2019. Selling, general and administrative (SG&A) expenses were $22.8 million in the third quarter of 2020, compared to SG&A expenses of $29.1 million in the third quarter of 2019.

GAAP net income for the third quarter of 2020 was $41.5 million, or $1.09 per diluted share, versus GAAP net income of $24.0 million, or $0.63 per diluted share, for the third quarter of 2019. This resulted in a net income margin of 18.0% and 11.1% for the third quarter of 2020 and 2019, respectively.

EBITDA for the third quarter of 2020 increased 49.4% to $51.9 million, or 22.5% of revenue, compared to $34.8 million, or 16.1% of revenue, for the comparable prior-year period. On a constant currency basis, EBITDA for the third quarter of 2020 increased 49.9% from the third quarter of 2019.

A reconciliation of the Company’s non-GAAP financial measures, including EBITDA and EBITDA margin to the corresponding GAAP measures is provided below.

Balance Sheet and Liquidity

The Company’s Cash and cash equivalents were $219.2 million at September 30, 2020, and the Company generated $59.8 million in cash flow from operating activities during the third quarter of 2020. The Company did not repurchase any shares during the third quarter.

The Company had $49.2 million remaining under its authorized share repurchase program at the end of the quarter. Additionally, the Company’s Board of Directors has authorized new share repurchases of the Company’s common stock in the open market or negotiated transactions, at the discretion of management, which brings the total current authorization back to $100 million. The extent and timing of repurchases depends on market conditions, applicable regulatory requirements, and other considerations. The share repurchase authorization does not obligate the Company to acquire any minimum amount of common stock and any repurchase program may be modified, limited, extended, suspended or terminated at any time at the Company’s discretion. The Company currently expects that any repurchases under the program would be made in compliance with the SEC’s Rules 10b-5 and 10b-18.

2020 Financial Guidance

The Company forecasts 2020 revenue in the range of $880.0 million to $920.0 million, representing growth of 2.2% to 6.9% over 2019 revenue of $861.0 million. GAAP net income for full year 2020 is forecasted in the range of $136.0 million to $144.0 million. Additionally, full year 2020 EBITDA is expected in the range of $180.0 million to $190.0 million. Based on forecasted 2020 revenue of $880.0 million to $920.0 million and GAAP net income of $136.0 million to $144.0 million, diluted earnings per share (GAAP) is forecasted in the range of $3.62 to $3.83. This guidance assumes a full year 2020 tax rate of 15.0% to 16.0% and does not reflect the potential impact of any share repurchases the Company may make pursuant to the share repurchase program.

2021 Financial Guidance

The Company forecasts 2021 revenue in the range of $1.050 billion to $1.125 billion. Full year 2021 EBITDA is expected in the range of $200.0 million to $220.0 million. The Company expects a 2021 full year tax rate of 16.0% to 20.0%.

Conference Call Details

Medpace will host a conference call at 9:00 a.m. ET, Tuesday, October 27, 2020, to discuss its third quarter 2020 results.

To participate in the conference call, dial 800-219-7113 (domestic) or 574-990-1030 (international) using the passcode 6989449.

To access the conference call via webcast, visit the "Investors" section of Medpace’s website at medpace.com. The webcast replay of the call will be available at the same site approximately one hour after the end of the call.

A supplemental slide presentation will also be available at the "Investors" section of Medpace’s website prior to the start of the call.

A recording of the call will be available at 12:00 p.m. ET on Tuesday, October 27, 2020 until 12:00 p.m. ET on Tuesday, November 10, 2020. To hear this recording, dial 855-859-2056 (domestic) or 404-537-3406 (international) using the passcode 6989449.

Castle Biosciences to Release Third Quarter 2020 Financial Results and Host Conference Call on Monday, November 9, 2020

On October 26, 2020 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported that it will release its financial results for the third quarter ended Sept. 30, 2020, after the close of market on Monday, Nov. 9, 2020 (Press release, Castle Biosciences, OCT 26, 2020, View Source [SID1234569066]).

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Company management will host a conference call and webcast to discuss its financial results and provide a corporate update at 4:30 p.m. Eastern time on the same day.

Conference Call and Webcast Details

A live webcast of the conference call can be accessed at View Source or via the webcast link on the Investor Relations page of the Company’s website (www.castlebiosciences.com). Please access the webcast at least 10 minutes before the conference call start time. An archive of the webcast will be available on the Company’s website until Nov. 30, 2020.

To access the live conference call via phone, please dial 877-282-2581 from the United States and Canada, or +1 470-495-9479 internationally, at least 10 minutes prior to the start of the call, using the conference ID 3586364.

There will be a brief Question & Answer session following the corporate update.